<i>IN SILICO</i> SCREENING

Abstract: A model structure of sub-domain IIId of the hepatitis C virus internal ribosome entry site has been elucidated. The invention provides an <i>in silico</i> method for identifying a compound that interacts with sub-domain IIId, comprising the steps of: a) providing atomic co-ordinates of said sub-domain IIId in a storage medium on a computer; and b) using said computer to apply molecular modelling techniques to said co-ordinates. Suitable methods include <i>de novo</i> compound design, use of a pharmacophore, and automated docking algorithms.

Description: INSILICO SCREENING All documents cited herein are incorporated by reference in their entirety. TECHNICAL FIELD This invention is in the field of in silico screening, more particularly the use of in silico methods to identify compounds that bind to sub-domain Illd of the hepatitis C virus genome. BACKGROUND ART Cap-independent translation of hepatitis C virus (HCV) genomic RNA is mediated by an internal ribosome entry site (IRES) within the 5'-UTR of the viral RNA, and inhibiting the interaction of translation initiation factors with the 5 -UTR has been proposed as a therapeutic strategy [e.g. references 1, 2 and 3]. Figure 1 shows the secondary structure of the 5'-UTR, which is divided into four major structural domains. Domains II, III and IV contribute to IRES translational activity, and are further sub-divided into stem-loops (e.g. Ila, lib etc.). No information concerning the tertiary structure of the IRES is presently available. The present invention concerns sub-domain Hid (nucleotides 253-279), which has been reported as critical for IRES folding and function [4]. It is highly conserved, with only two sequence differences (co-variant alterations) between the various HCN genotypes. Sub-domain Illd is thus proposed as a drug target, and it is an object of the invention to facilitate the in silico identification and design of compounds that interact with sub-domain Illd, with a view to inhibiting IRES-mediated translation. DISCLOSURE OF THE INVENTION The invention is based on the elucidation of a model structure of sub-domain Illd. This contains several unexpected structural motifs, and is readily applicable to in silico drug design. The invention provides an in silico method for identifying a compound that interacts with sub-domain Hid of the hepatitis C virus IRES, comprising the steps of: (a) providing atomic co-ordinates of said sub-domain Hid in a storage medium on a computer; and (b) using said computer to apply molecular modelling techniques to said co-ordinates. The atomic co-ordinates The invention involves the use of atomic co-ordinates of sub-domain Hid. These may be co-ordinates for the complete sub-domain Hid (nucleotides 253-279), they may be co-ordinates for a fragment of the IRES that comprises sub-domain Illd, or they may be co-ordinates for a fragment of sub-domain Illd. Preferred atomic co-ordinates for use according to the invention are ιιid_gc . pdb and ιιid_gu . pdb, as set out herein. Both these co-ordinate sets represent the complete 27mer sub-domain Hid. The two sets are for the two polymorphic Hid sequences found in nature, and were determined by NMR in combination with molecular modelling and phylogenetic data. Variants of ιιid_gc .pdb and ιιid_gu.pdb can also be used for the invention, such as variants in which the r.m.s. deviation of the x, y and z co-ordinates for all heavy (i.e. not hydrogen) atoms are all less than 2.5A (e.g. less than 2A, preferably less than lA, and more preferably less than 0.5A or less than 0.1 A) compared with the structures given herein. Preferred fragments of sub-domain Illd whose co-ordinates can be used in the invention are: - the ' Sarcin/Ricin loop' (SRL) motif (nucleotides A257, G258, U259, A260, G273, A274, A275); - the 'trans-wobble' base pair (nucleotides U264, G268); and - the terminal loop (nucleotides U264, U265, G266, G267, G268, U269). Because of the similarity of the SRL motif to elements in human rRNA, however, a drug targeted to it may- exhibit toxicity to human cells. Similarly, the terminal loop contains a fragment similar to the 'T-loop' of Phe-tRNA. A more preferred fragment of sub-domain Hid whose co-ordinates can be used according to the invention thus comprises both of these motifs (i.e. nucleotides A257, G258, U259, A260, U264, U265, G266, G267, G268, U269, G273, A274, A275), as their juxtaposition is not native to human RNA. The anti-anti trans-wobble U264*G268 pair in the terminal loop has not so far been observed in RNAs whose structures have been solved, offering further specificity. The storage medium The storage medium in which the atomic co-ordinates are provided is preferably random- access memory (RAM), but may also be read-only memory (ROM e.g. CDROM), or a diskette. The storage medium may be local to the computer, or may be remote (e.g. a networked storage medium, including the internet). The invention also provides a computer-readable medium for a computer, characterised in that the medium contains atomic co-ordinates of sub-domain Hid of the hepatitis C virus IRES. The atomic co-ordinates are preferably iιid_gc . pdb or nid_gu . pdb, or variants thereof. Any suitable computer can be used in the present invention. Molecular modelling techniques Molecular modelling techniques can be applied to the atomic co-ordinates of sub-domain Illd structure to derive a range of 3D models and to investigate the structure of ligand binding sites. A variety of molecular modelling methods are available to the skilled person for use according to the invention [e.g. ref. 5]. At the simplest level, visual inspection of a computer model of sub-domain Hid can be used, in association with manual docking of models of functional groups into its binding pockets. Software for implementing molecular modelling techniques may also be used. Typical suites of software include CERIUS2 [6], SYBYL [7], AMBER [8], HYPERCHEM [9], INSIGHT II [6], CATALYST [6], CHEMSITE [10], QUANTA [6]. These packages implement many different algorithms that may be used according to the invention (e.g. CHARMm molecular mechanics [11]). Their uses in the methods of the invention include, but are not limited to: (a) interactive modelling of the structure with concurrent geometry optimisation (e.g. QUANTA); (b) molecular dynamics simulation of sub-domain Illd structure (e.g. CHARMM, AMBER); (c) normal mode dynamics simulation of sub-domain Hid structure (e.g. CHARMM). Modelling may include one or more steps of energy minimisation with standard molecular mechanics force fields, such as those used in CHARMM and AMBER. These molecular modelling techniques allow the construction of structural models that can be used for in silico drug design and modelling. Some algorithmic techniques listed above are conventionally used for modelling ligand- protein interactions, but can be modified for modelling ligand-RNA interactions for use according to the present invention. de novo compound design The molecular modelling steps used in the methods of the invention may use the atomic co-ordinates of sub-domain Hid, and models derived therefrom, to determine binding surfaces. This preferably reveals van der Waals contacts, electrostatic interactions, and/or hydrogen bonding opportunities. These binding surfaces will typically be used by grid-based techniques (e.g. GRID [12], CERIUS2) and/or multiple copy simultaneous search (MCSS) techniques [13] to map favourable interaction positions for functional groups. This preferably reveals positions in sub-domain Hid for interactions such as, but not limited to, those with protons, hydroxyl groups, amine groups, hydrophobic groups (e.g. methyl, ethyl, benzyl) and/or divalent cations. Once functional groups or small molecule fragments which can interact with specific sites in the binding surface of sub-domain Hid have been identified, they can be linked in a single compound using either bridging fragments with the correct size and geometry or frameworks which can support the functional groups at favourable orientations, thereby providing a compound according to the invention. Whilst linking of functional groups in this way can be done manually, perhaps with the help of software such as QUANTA or SYBYL, the following software may be used for assistance: HOOK [6], which links multiple functional groups with moleculai- templates taken from a database, and/or CAVEAT [14], which designs linking units to constrain acyclic molecules. Other computer-based approaches to de novo compound design that can be used with the Hid atomic co-ordinates include LUDI [15,6], SPROUT [16] and LEAPFROG [7]. Pharmacophore searching As well as using de novo design, a pharmacophore of sub-domain Hid can be defined i.e. a collection of chemical features and 3D constraints that expresses ' specific characteristics responsible for biological activity. The pharmacophore preferably includes surface-accessible features, more preferably including hydrogen bond donors and acceptors, charged/ionisable groups, and/or hydrophobic patches. These may be weighted depending on their relative importance in conferring activity [17]. Pharmacophores can be determined using software such as CATALYST (including HypoGen or HipHop) [6], CERIUS2, or constructed by hand from a known conformation of a lead compound. The pharmacophore can be used to screen in silico compound libraries, using a program such as CATALYST [6]. Suitable in silico libraries include the Available Chemical Directory (MDL Inc), the Derwent World Drug Index (WDI), BioByteMasterFile, the National Cancer Institute database (NCI), and the Maybridge catalog. Docking Compounds in these in silico libraries can also be screened for their ability to interact with sub-domain Illd by using their respective atomic co-ordinates in automated docking algorithms. Suitable docking algorithms include: DOCK [18], AUTODOCK [19,8], MOE-DOCK [20] or FLEXX [7]. Docking algorithms can also be used to verify interactions with ligands designed de novo. Homology models Several proteins have been identified which bind to RNAs containing elements related to the loop E motif family [reviewed in ref. 29]. They include, among others, the bacterial ribosomal protein L25 and the eukaryotic ribosomal protein L5. These proteins may bind to the SRL motif within sub-domain Hid, or can be engineered to do so, and can be used in two ways: 1. To design a reporter for a displacement assay for the identification of ligands binding to HCV sub-domain Hid. A protein, or a fragment thereof, which binds to sub-domain Hid can be used in an assay for the interaction e.g. using FRET (e.g. WO99/64625), chemical footprinting, or retardation of mobility in gel electrophoresis. Compounds produced through a drug discovery program could then be assayed for their ability to disrupt this protein-RNA interaction, as an indication of binding to sub-domain Hid. 2. To design libraries of compounds for a drug discovery program targeted at binding to HCV sub-domain Hid. Whilst the native proteins and fragments may not have optimal properties for pharmaceutical use, the structure of the complex of the protein with the substrate prokaryotic loop E or SRL type RNA [c.f. 21] can be used to identify elements which interact with the RNA. These elements can be mimicked by a compound (e.g. in a library designed with knowledge of structure underlying the interaction). In both cases, the co-ordinates of the invention can be used to perfect the design as follows: - the designed reporter or compound is docked against the co-ordinates of the invention, by analogy with the interaction observed in the analogous prokaryotic loop E or SRL type motif in the known crystal or NMR structure(s); - fragments and/or functional groups from the protein which are suitable for the design of a low molecular weight compound are identified, as well as possible contacts or clashes with other parts of the Hid RNA; - the reporter or compound is then modified to alleviate steric or electrostatic clashes, reduce the molecular weight, improve pharmacological properties, and/or add favourable interactions by means described above. Typical compounds designed in this way may be fragments from a protein, small organic molecules containing the critical functional groups, or "antisense" ligands (e.g. PNAs, oligonucleotides, etc.) Similar methods can be used to design a reporter or compound library to interact with the terminal loop, based on analogies to the T-loop of tRNA (which interacts with the tRNA D-loop), tobramycin (which interacts with an RNA aptamer containing a U-turn [22]), or other homologous RNAs from viral or bacterial systems. It will be appreciated that these techniques can be applied to any RNA which contains these structural motifs, not just sub-domain Hid of the HCV IRES. 'Dual site' design A compound identified using the invention preferably interacts with one or more nucleotides from the 'loop E' motif (A257, G258, U259, A260, G273, A274, A275) and one or more nucleotides from the terminal loop (U264, U265, G266, G267, G268, U269). These two regions contain homologies to human RNA structures and, as it is believed that sub-domain Hid functions in vivo by mimicking these structures and thereby sequestering cellular proteins, a compound that interacts with only one of these two regions may be toxic to the host. As the juxtaposition of these motifs appears to be unique to HCV, however, targeting them both simultaneously will allow specificity. Moreover, the U264»G268 pair adds further specificity. In general, the design strategy begins by searching for ligands with relatively weak affinity to each of these two sites. Linking these two ligands in order to permit their simultaneous interaction with the target typically increases affinity by orders of magnitude. Moreover, the RNA regions between the terminal loop and the loop E motif contain distinctive features which can be recognised by an appropriate linker, such as the U264-G268 pair, adding further specificity and affinity. Basis for further models The atomic co-ordinates of the invention can be used as the basis of models of further RNA structures. For example, a homology model of a RNA structure could be based on the sub-domain Illd structures of the present invention. Furthermore, the structures of fragments of the sub-domain Hid model can be used as the basis of modelling equivalent structures in other RNA molecules. Where a RNA molecule is thought to contain a loop E motif, for instance, the structure of nucleotides A257, G258, U259, A260, G273, A274, & A275 of HCV sub-domain Hid can be used as a template. Similarly, the 'trans- wobble' base pair (nucleotides U264, G268) of sub-domain Hid can be used as the basis of a model. Testing compounds The methods of the invention may comprise the further steps of: (c) providing a compound identified by said molecular modelling techniques; and (d) contacting said compound with the HCV IRES and assaying the interaction between them. Suitable methods for assaying the interaction between the HCV IRES and the compound include: (i) the direct methods disclosed in WO99/64625; (b) the indirect methods disclosed in references 23 and 24.- Preferred indirect methods use bicistronic constructs containing two different luciferases, the first being translated in a cap-dependent manner and the second being translated from the HCV IRES tin a cap-independent -manner. The relative levels of the two luciferases gives an indication of whether the IRES-mediated translation was inhibited. Compounds and their uses The methods of the invention identify compounds that can interact with sub-domain Hid of the hepatitis C virus IRES. These compounds may be designed de novo, may be known compounds, or may be based on known compounds. The invention also provides: (i) a compound identified using the methods of the invention; (ii) a compound identified using the methods of the invention for use as a pharmaceutical; (iii) the use of a compound identified using the methods of the invention in the manufacture of a medicament for treating hepatitis C infection; and (iv) a method of treating a patient with hepatitis C infection, comprising administering an effective amount of a compound identified using the methods of the invention. BRIEF DESCRIPTION OF DRAWINGS Figure 1 shows the HCV IRES, including secondary structural motifs. Sub-domain Hid is enlarged and boxed. Figure 2 shows the construct used to assess mutant IRES activity. Figure 3 shows various motifs from the 'loop E' or 'SRL' family. 3A shows the sarcin/ricin (SRL) loop and chemical shifts, and 3B shows the prokaryotic 5S rRNA loop E. In 3C, these structures are mapped onto HCV sub-domain Hid. Figure 4 shows example NMR spectra from sub-domain Hid. 4A shows the region of a NOESY (150ms mixing time) spectrum acquired in H 2 O, illustrating NOEs between imino proton and aromatic/amino proton resonances. 4B shows the region of a NOESY (120ms mixing time) spectrum acquired in D 2 O, illustrating NOEs between aromatic proton resonances, with the characteristic NOE between the H2 proton resonances of A260 and A274 highlighted. 4C shows a natural-abundance ! H- 13 C HMQC spectrum. Positive peaks (predominantly to the left) are darker than the negative peaks (predominantly to the right). Figure 5 highlights NMR signals from the terminal loop region. 5A shows the imino-imino proton region of NOESY in H 2 O. 5B shows the aromatic to anomeric proton NOESY at 400ms which establish the relative geometries of nucleotides G268 and C270. Figure 6 shows the two sub-domain Hid sequences for which 3D structures were produced. MODES FOR CARRYING OUT THE INVENTION Mutational analysis of sub-domain Hid Substitution mutants of sub-domain Hid were created using oligonucleotide site-directed mutagenesis using the Stratagene QuickChange Kit™. The template plasmid was pTZ18:5442-l6-l, which contains the HCV la 5'-UTR (nucleotides 18-357) in the BamHI site of pTZ18U [25]. Mutant derivatives of the 5'-UTR were sub-cloned into the BamHI site of dual reporter pRT9, constructed as follows: (i) pRTl was constructed by deleting the BamHI site of pRL-NulI (Promega) using Klenow; (ii) the EcoRV/Hindlll fragment of pD5(3.3) [26] was inserted into BglII(blunt)/HindIII digested pRTl, to give pRT2; (iii) the SacI/HindlH blunt-ended fragment of pRL-5442-16-1 [24] was inserted into pRT2 digested with Nhel/Xbal and blunt-ended. pRT9 thus contains the HIV-1 LTR (nucleotides -340 to +78) and transcribes a bicistronic mRNA encoding renilla luciferase, the HCV 5'-UTR, and firefly luciferase (Figure 2). The ratio of renilla and firefly luciferases indicates the activity of the IRES in the 5'-UTR. To assay the relative activities, 35cm 2 dishes were seeded with 2xl0 5 C63 HeLa cells. After 24 hours, transfections were performed with lμg pRT9 (or mutant) using CaPO 4 . After 40 hours, cells were harvested, lysed and assayed for both luciferases using the Promega dual-luciferase assay (following manufacturer's instructions), and results were as follows: Replacing the terminal hexaloop (264-269) with a tetraloop sequence abolishes IRES activity. To investigate this in further detail, dual substitution mutants for 264 U and 69 U were constructed and, consistent with the tetraloop mutant, IRES activity was significantly diminished. Replacing the AA dinucleotide (275-276) with CUC, thereby converting the internal loop into a double helix, also reduced IRES activity. Single point mutants at residues 260 and 276 within the internal loop, gave similar results, as did insertions. The terminal and internal loops in Hid are thus crucially important for IRES activity. Modelling the Hid structure - hypothesis The internal loop within Hid contains a sequence almost identical to that in the sarcin/ricin loop fragment [27], which forms a 'loop E' motif structure [e.g. 28, 29, 30, 31, 32, " 33, 34]. It was thus hypothesised that the internal loop of Hid would fold in the same manner. Examples of the 'loop E' or 'SRL' motif family have been observed in the eukaryotic 5S rRNA loop E and in the sarcin/ricin loop (figure 3A) from rRNA, where it is universally conserved. Another example is present in the prokaryotic 5S rRNA loop E (figure 3B), but this lacks the bulged-out nucleotide and, furthermore, is present as tandem copies. The SRL motif within the sarcin/ricin loop itself gives rise to a number of unusual chemical shifts (figure 3A): 8.6ppm for the H8 proton of A9, 81.3ppm for the Cl' resonance of G10, and just over 4ppm for the anomeric protons of the C13-G18 base pair. In addition, distinct pairs of amino proton resonances appear associated with purines in the SRL motif. Amino resonances from A9 appear at 8.72ppm and 6.72ppm, similar to shifts observed for amino resonances in Watson-Crick paired regions, but the A20 aminos resonate at 6.45ppm and 6.82ppm. Distinctive NOE patterns are predicted from the non-canonical base-pairing schemes shown in figure 3A e.g. the reverse trans-Hoogsteen Ul 1»A20 base pair will give rise to NOEs between the imino proton of Ul l and the H8 and amino protons of A20. Based on the hypothesis, analogous NOEs were predicted between U259 and A274 of sub-domain Hid. In addition, an exceptionally intense cross-strand NOE is seen in the SRL between the H2 protons of A20 and A 12, due to the unusual geometry of the motif. An analogous NOE between A260 and A274 of sub-domain Hid was predicted. The reversal in strand direction between A10 and U12 in the SRL is known as an 'S -motif or 'S-turn'. NMR was used to test the hypothesis. NMR spectra A 27mer RNA identical in sequence to sub-domain Hid of the HCV IRES was synthesised by T7 RNA polymerase transcription from synthetic DNA templates [35]. Transcripts were purified on 20% polyacrylamide gels containing 7M urea [36], and full-length transcripts were excised from the gels, electro-eluted, and dialysed into 8mM sodium phosphate buffer, pH 6.6. Addition of sodium or magnesium chloride has no significant effect on the NMR spectra, and was thus not included in the sample buffer. Final concentration in NMR samples was 1.2mM RNA in 200μl volume. NMR spectra were recorded on Bruker DRX500 and DMX600 spectrometers. For analysis of exchangeable protons, NOESY experiments were run at 5°C and 25°C. A jump-return- WATERGATE sequence was used for water suppression [37]. The sample was lyophilised and re-suspended in D 2 O for non-exchangeable proton assignment. NOESY (60, 120, 150 and 400ms mixing times), TOCSY and COSY-DQF experiments were run at 20°C and 30°C. Proton-phosphorus and proton-carbon (natural abundance) carbon heteronuclear correlation experiments, ! H- 31 P-COSY, 1H- 31 P-hetero-TOCSY and Η- 13 C-HMQC were performed at 30°C. Proton chemical shifts were referenced to the residual water peak (4.77ppm at 25°C). As shown in figure 4 A, a pair of NOE signals appears near 6.5ppm, arising from amino resonances of A274. A sharp cross-peak near 7.5ppm demonstrates a close contact between U259 imino (12.5ppm) and A274 H8 (7.5ppm), confirming the predicted trans-Hoogsteen base pair. At the contour level shown in figure 4B, two aromatic-aromatic NOEs are visible. The A274 H2 to A260 H2 NOE cross-peak, analogous to the intense cross-strand NOE (A20 & A 12) seen in the SRL, is indicated. In figure 4C, two anomalous HI' proton shifts (G261 & G277 HI') and one unusual Cl' carbon shift (G258 Cl') are seen in positions strikingly similar to those observed in the SRL. Together, these data confirm that the overall fold and the base pairings in this region of Hid are the same as those of the SRL. The hypothesis was correct. Additional data from NMR spectra As well as confiπning the SRL motif for the Hid internal loop, the NMR spectra suggested further structural elements. U269 bulge The aromatic to anomeric protein NOE connectivity path in Hid is broken between nucleotides G268 and C270, which show NOEs to each other (i.e. base stacking) in both directions (figure 5A). A similar 'box pattern' of NOEs can arise where alternating anti and syn glycosidic angles are present, as in Z-D A [38] or 'foldback' G-quartet structures [39]. In the absence of the diagnostic signals associated with syn glycosidic geometry, however, this pattern can only arise in Hid from a localised backbone inversion at G268. This inversion in accommodated by, and dependent upon, the bulged-out nucleotide U269, indicated by U269 only presenting intranucleotide cross-peaks. . The presence of a locally inverted nucleotide 5' to a bulged-out nucleotide has been reported in several structures, including the RRE [40] and the loop E motif of the SRL. G268-U264 'trans- wobble' base pair The formation of a G268 « U264 base pair, is indicated by imino proton resonances at 10.9ppm (G268H1) and l l .βppm (U264H3), as shown in figure 5B. Considering the backbone inversion at the position of G268, this base pair must be of a locally parallel trans type, involving hydrogen bonding between G268H1 & U264O4 and G268O6 & U264H3. Both of these imino resonances show NOEs to each other and to G263H1, consistent with stacking of the U264-G268 pair on the G263 » C270 pair. A 'trans-wobble' G«U base pair has been observed previously in the crystal structure of a fragment of the hepatitis delta virus ribozyme, albeit with the G in the syn conformation [41]. 'U-turn' motif With U264 and G268 forming a base pair, the backbone turn in the Hid terminal loop must be accomplished by U265, G266 and G267 only. These three residues are predicted to form a 'U-turn' -motif [42,43]. Sharp turns in nucleic acid helices require major distortions in backbone torsion angles from those found in helical regions. A set of characteristic torsion angles was observed in the first tRNA crystal structures, especially within loop regions. The distortion is localised at the α and ξ torsion angles in three phosphate residues in the loop. Similar results have been seen in crystal and NMR structures of RNA [44, 45, 46, 47]. This motif is referred to as the 'U-turn', and is often associated with a uracil residue which stacks on the i+2 phosphate (the 'stacking phosphate') while hydrogen bonding to oxygen on the i+3 phosphate (the Η-bonding phosphate'). All observed proton-proton NOEs for Hid are consistent with this motif, and the U265-P- G266. G266-P-G267 and G267-P-G268 chemical shifts are in the predicted order relative to each other. Conclusion Overall, there are no unassigned imino, amino or aromatic resonances, the presence of which would indicate the formation of alternative or unfolded structures. In isolation, the 27mer Hid fragment forms an exceptionally stable secondary structure, which is likely to be maintained within the context of the full HCV 5'-UTR. In particular, 'loop E' motifs seen in rRNA are maintained in the presence of ribosomal proteins [48], and 'U-turn' motifs seen in tRNAs and in the GTPase centre hexaloop are maintained in the presence of tertiary interactions with other RNA loops. Modelling sub-domain Illd The NMR data was used in conjunction with a motif-based approach in order to construct a model of the three-dimensional structure of sub-domain Hid. Six motifs were used: (i) an A-form double helix (ii) a sheared G » A base pair (iii) a SRL motif (iv) a localised backbone inversion (v) a trans-wobble G'U base pair (vi) a U-turn The presence of each of these six motifs has experimental basis in the NMR spectra. Examples of motifs (ii)-(iv) & (vi) were extracted from NMR and crystal PDB structures. Motifs (ii) and (iii) were taken from the SRL structure [430D .pdb, ref. 49]. Motif (iv) was extracted from the RRE structure [lETG . pdb, ref. 40]. Motif (vi) was extracted from the GTPase RNA structure [iQA6. P db, ref. 47]. Motif (i) was built using idealised co-ordinates (InsightH biopolymer module [6]), and motif (v) was generated with InsightH using idealised base planarity and hydrogen-bonding distances and angles. The motifs were ligated together in silico as follows. The G253 to C255 double helix was constructed using InsightH. A sheared G256 » A276 base pair was added manually using InsightH, maintaining acceptable C255O3'-G256P and G277P-A276O3' distances. The A257- A260 and G273-A275 loop E motif was then positioned. Idealised A-form co-ordinates were then used to build the G261-G263 double helix, with some manual adjustment to incorporate the U262*G271 base pair. The backbone inversion at G268/U269 was then positioned in such a way as to optimise G268-C270 stacking and to allow a suitable G268 orientation for the positioning of U264. Using A-form co-ordinates, U264 was positioned to stack on G263 and form a trans-wobble pair with G268. The U-turn motif was then positioned to complete the loop sequence between U264 and G268. All the components of the model were ligated using the InsightH biopolymer module and the resulting structure was energy minimised using Charmm 25. a2 to remove unfavourable bond lengths and angles. The resulting structure is given below as 11 id_gc . pdb. Taking into account the natural polymorphism in HCV, the same procedure was followed for a sub-domain Illd having the sequence 262 CGUUGGGUUG 271 instead of 262 UGUUGGGUCG 271 (see figure 6). This structure is given below as ιιid__gu . pdb. These models were carefully analysed to ensure conformity with the NMR spectra. The A-form helix and loop E motif could be directly compared with published NMR data and were in extremely good agreement. A list of all probable and improbable NOEs expected from these terminal loop region of the model was compared to the NMR data and in all cases the model and NMR were consistent. 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(1998) PNAS USA 95:13436-441. u & θ θ o o o o u 2 θ s o s s υ o o s o υ o o o -c --; a 3 , E a- 3, -q w P-! 3» α-; c ^ o o o o o o u 2 θ o θ ϊs ) 2; υ υ o ^r , O *=r j ^r i -n r-- r-- -π -n -o C-J O O O O O O rH rH tD r- r— σι σι σi H m r- ri ( -i cM ^r ^ rH ∞ r- r~ -n ^r l >5r' -n r r ) CM i-H r-) r-- co m m m co r— lo in m « \» in -o CM CM C^ CM CM CM CM CM CM CM CM CM EH EH EH EH EH EH EH >H >H H >H H H H >H CJ O CJ O o CD CJ J CJ CJ CJ CJ CJ O O U O . - ci ^ -n -n -n -n o 2 PC ATOM 56 03' CYT 254 12..919 8.982 3.021 0.00 58.24 0 ATOM 57 1H5' CYT 254 14. .250 8.970 6.940 0.00 0.00 H ATOM 58 2H5' CYT 254 12. .793 9.303 5.930 0.00 0.00 H ATOM 59 H4' CYT 254 14. .903 9.597 4.627 0.00 0.00 H ATOM 60 HI' CYT 254 16. .987 7.275 3.483 0.00 0.00 H ATOM 61 H6 CYT 254 14. .576 5.555 5.586 0.00 0.00 H ATOM 62 1H4 CYT 254 15. ,115 1.003 4.908 0.00 0.00 H ATOM 63 2H4 CYT 254 • 16. ,056 0.819 3.460 0.00 0.00 H ATOM 64 H5 CYT 254 14. ,409 3.103 5.774 0.00 0.00 H ATOM 65 H2' CYT 254 14. ,733 6.954 1.926 1.00 0.00 H ATOM 66 H02' CYT 254 14. ,837 9.293 1.721 0.00 0.00 H ATOM 67 H3' CYT 254 13. .271 7.074 3.885 0.00 0.00 H ATOM 68 P CYT 255 11. .514 8.530 2.443 0.00 58.36 P ATOM 69 OIP CYT 255 10. .721 9.742 2.135 0.00 58.73 0 ATOM 70 02P CYT 255 10. ,904 7.533 3.351 0.00 57.89 0 ATOM 71 05' CYT 255 11. .907 7.811 1.086 0.00 58.47 0 ATOM 72 C5' CYT 255 12. .346 8.631 0.005 0.00 59.01 c ATOM 73 C4' CYT 255 13. ,066 7.819 -1.082 0.00 59.66 c ATOM 74 04' CYT 255 14. .173 7.038 -0.524 0.00 59.98 0 ATOM 75 Cl' CYT 255 14. .257 5.775 -1.208 0.00 60.44 c ATOM 76 Nl CYT 255 14. ,014 4.598 -0.300 0.00 0.00 N ATOM 77 C6 CYT 255 13. .387 4.667 0.941 0.00 0.00 c ATOM 78 C2 CYT 255 14. ,334 3.307 -0.839 0.00 0.00 C ATOM 79 02 CYT 255 14. .845 3.184 -1.967 0.00 0.00 0 ATOM 80 N3 CYT 255 14. ,054 2.191 -0.081 0.00 0.00 N ATOM 81 C4 CYT 255 13. ,479 2.281 1.143 0.00 0.00 C ATOM 82 N4 CYT 255 13. ,240 1.169 1.894 0.00 0.00 N ATOM 83 C5 CYT 255 13, ,116 3.574 1.673 0.00 0.00 C ATOM 84 C2' CYT 255 13, .246 5.868 -2.363 0.00 60.12 C ATOM 85 02' CYT 255 13, .854 6.446 -3.518 0.00 59.65 0 ATOM 86 C3' CYT 255 12. .191 6.773 -1.748 0.00 60.02 c ATOM 87 03' CYT 255 11. .326 7.329 -2.739 0.00 59.53 0 ATOM 88 1H5' CYT 255 13. .048 9.422 0.359 0.00 0.00 H ATOM 89 2H5' CYT 255 11. .466 9.135 -0.455 0.00 0.00 H ATOM 90 H4' CYT 255 13. .504 8.505 -1.839 0.00 0.00 H ATOM 91 HI' CYT 255 15. .290 5.714 -1.614 0.00 0.00 H ATOM 92 H6 CYT 255 13, .118 5.658 1.294 0.00 0.00 H ATOM 93 1H4 CYT 255 13. ,501 0.271 1.536 0.00 0.00 H ATOM 94 2H4 CYT 255 12. ,811 1.250 2.793 0.00 0.00 H ATOM 95 H5 CYT 255 12. .634 3.646 2.649 0.00 0.00 H ATOM 96 H2' CYT 255 12. .876 4.878 -2.630 1.00 0.00 H ATOM 97 H02' CYT 255 13. ,126 6.823 -4.019 0.00 0.00 H ATOM 98 H3' CYT 255 11, .640 6.204 -0.960 0.00 0.00 H ATOM 99 P GUA 256 9, .835 6.802 -2.848 0.00 59.25 P ATOM 100 OIP GUA 256 9, .181 7.458 -4.001 0.00 59.56 O ATOM 101 02P GUA 256 9 .183 6.936 -1.526 0.00 59.17 O ATOM 102 05' GUA 256 10, .014 5.259 -3.163 0.00 59.81 O ATOM 103 C5' GUA 256 10, .503 4.868 -4.441 0.00 60.87 c ATOM 104 C4' GUA 256 10, .741 3.349 -4.526 0.00 61.59 c ATOM 105 04' GUA 256 11, .604 2.863 -3.450 0.00 61.62 O ATOM 106 Cl' GUA 256 11, .138 1.579 -3.005 0.00 62.16 c ATOM 107 N9 GUA 256 10, .740 1.655 -1.566 0.00 0.00 N ATOM 108 C4 GUA 256 10 .729 0.581 -0.653 0.00 0.00 C ATOM 109 N3 GUA 256 11 .115 -0.706 -0.869 0.00 0.00 N ATOM 110 C2 GUA 256 11, .038 -1.506 0.236 0.00 0.00 C ATOM 111 Nl GUA 256 10, .552 -0.997 1.455 0.00 0.00 N ATOM 112 N2 GUA 256 11 .412 -2.813 0.321 0.00 0.00 N ATOM 113 C6 GUA 256 10 .126 0.338 1.694 0.00 0.00 C ATOM 114 06 GUA 256 9 .719 0.737 2.791 0.00 0.00 O ATOM 115 C5 GUA 256 10 .254 1.127 0.544 0.00 0.00 C ATOM 116 N7 GUA 256 9.977 2.455 0.401 0.00 0.00 N ATOM 117 C8 GUA 256 10.278 2.722 -0.843 0.00 0.00 C ATOM 118 C2' GUA 256 9.996 1.178 -3.968 0.00 62.12 C ATOM 119 02' GUA 256 10.511 0.466 -5.091 0.00 62.53 O ATOM 120 C3' GUA 256 9.466 2.551 -4.356 0.00 61.95 C ATOM 121 03' GUA 256 8.706 2.563 -5.564 0.00 62.47 O ATOM 122 1H5' GUA 256 11.463 5.384- -4.665 0.00 0.00 H ATOM 123 2H5' GUA 256 9.768 5.153 -5.228 0.00 0.00 H ATOM 124 H4' GUA 256 11.244 3.094 -5.484 0.00 0.00 H ATOM 125 HI' GUA 256 11.992 0.877 -3.109 0.00 0.00 H ATOM 126 HI GUA 256 10.488 -1.616 2.250 0.00 0.00 H ATOM 127 1H2 GUA 256 11.338 -3.310 1.186 0.00 0.00 H ATOM 128 2H2 GUA 256 11.791 -3.275 -0.485 0.00 0.00 H ATOM 129 H8 GUA 256 10.198 3.695 -1.320 0.00 0.00 H ATOM 130 H2' GUA 256 9.272 0.539 -3.462 1.00 0.00 H ATOM 131 H02' GUA 256 9.860 0.595 -5.787 0.00 0.00 H ATOM 132 H3' GUA 256 8.897 2.961 -3.488 0.00 0.00 H ATOM 133 P ADE 257 7.127 2.602 -5.486 0.00 62.88 P ATOM 134 OIP ADE 257 6.659 1.442 -4.698 0.00 63.83 O ATOM 135 02P ADE 257 6.590 2.758 -6.856 0.00 62.66 O ATOM 136 05' ADE 257 6.869 3.938 -4.676 0.00 63.40 O ATOM 137 C5' ADE 257 5.537 4.421 -4.524 0.00 63.28 C ATOM 138 C4' ADE 257 5.115 4.544 -3.048 0.00 63.36 C ATOM 139 04' ADE 257 5.148 3.239 -2.385 0.00 63.11 O ATOM 140 Cl' ADE 257 5.828 3.381 -1.147 0.00 63.28 C ATOM 141 C5 ADE 257 6.778 0.290 0.591 0.00 66.07 C ATOM 142 N7 ADE 257 7.236 -0.010 -0.665 0.00 65.10 N ATOM 143 C8 ADE 257 6.949 1.059 -1.370 0.00 64.65 C ATOM 144 N9 ADE 257 6.312 2.052 -0.679 0.00 64.25 N ATOM 145 Nl ADE 257 6.300 0.141 2.882 0.00 66.66 N ATOM 146 C2 ADE 257 5.777 1.366 2.783 0.00 66.11 C ATOM 147 N3 ADE 257 5.666 2.158 1.716 0.00 65.82 N ATOM 148 C4 ADE 257 6.205 1.555 0.628 0.00 65.45 C ATOM 149 C6 ADE 257 6.828 -0.473 1.775 0.00 66.44 C ATOM 150 N6 ADE 257 7.382 -1.721 1.755 0.00 67.16 N ATOM 151 C2' ADE 257 6.907 4.422 -1.454 0.00 63.16 C ATOM 152 02' ADE 257 7.540 4.949 -0.290 0.00 62.46 O ATOM 153 C3' ADE 257 6.075 5.437 -2.247 0.00 63.12 c ATOM 154 03' ADE 257 5.370 6.308 -1.367 0.00 63.80 O ATOM 155 1H5' ADE 257 4.785 3.794 -5.058 0.00 0.00 H ATOM 156 2H5' ADE 257 5.486 5.434 -4.981 0.00 0.00 H ATOM 157 H4' ADE 257 4.067 4.905 -3.002 0.00 0.00 H ATOM 158 HI' ADE 257 5.086 3.801 -0.432 0.00 0.00 H ATOM 159 H8 ADE 257 7.178 1.219 -2.420 0.00 0.00 H ATOM 160 H2 ADE 257 5.382 1.779 3.712 0.00 0.00 H ATOM 161 1H6 ADE 257 7.512 -2.226 2.612 0.00 0.00 H ATOM 162 2H6 ADE 257 7.733 -2.095 0.894 0.00 0.00 H ATOM 163 H2' ADE 257 7.721 4.039 -2.069 1.00 0.00 H ATOM 164 H02' ADE 257 8.043 5.715 -0.593 0.00 0.00 H ATOM 165 H3' ADE 257 6.740 6.021 -2.922 0.00 0.00 H ATOM 166 P GUA 258 4.616 7.593 -1.897 0.00 63.26 P ATOM 167 OIP GUA 258 4.948 7.829 -3.320 0.00 63.23 O ATOM 168 02P GUA 258 4.841 8.708 -0.950 0.00 63.92 O ATOM 169 05' GUA 258 3.100 7.135 -1.796 0.00 63.46 O ATOM 170 C5' GUA 258 2.590 6.758 -0.517 0.00 63.77 c ATOM 171 C4' GUA 258 1.899 5.399 -0.628 0.00 64.66 c ATOM 172 04' GUA 258 1.788 4.796 0.702 0.00 64.79 O ATOM 173 Cl' GUA 258 0.416 4.521 0.957 0.00 64.83 C ATOM 174 N9 GUA 258 0.192 4.387 2.418 0.00 64.48 N ATOM 175 C4 GUA 258 0.711 3.355 3.209 0.00 64.11 C ATOM 176 N3 GUA 258 1.542 2.357 2.816 0.00 63.91 N ATOM 177 C2 GUA 258 1.917 1.521 3.814 0.00 63.72 C ATOM 178 Nl GUA 258 1.421 1.691 5.121 0.00 64.00 N ATOM 179 N2 GUA 258 2.786 0.487 3.688 0.00 63.25 N ATOM 180 C6 GUA 258 0.531 2.718 5.548 0.00 64.06 C ATOM 181 06 GUA 258 0.132 2.832 6.712 0.00 63.17 O ATOM 182 C5 GUA 258 0.199 3.575 4.488 0.00 64.23 C ATOM 183 N7 GUA 258 -0.608 4.680 4.502 0.00 64.22 N ATOM 184 C8 GUA 258 -0.592 5.116 3.265 0.00 64.55 C ATOM 185 C2' GUA 258 -0.298 5.648 0.210 0.00 64.98 C ATOM 186 02' GUA 258 -1.712 5.498 0.149 0.00 65.30 O ATOM 187 C3' GUA 258 0.453 5.530 -1.124 0.00 65.31 C ATOM 188 03' GUA 258 0.161 4.345 -1.854 0.00 66.59 0 ATOM 189 1H5' GUA 258 1.869 7.530 -0.171 0.00 0.00 H ATOM 190 2H5' GUA 258 3.388 6.687 0.262 0.00 0.00 H ATOM 191 H4' GUA 258 2.505 4.706 -1.250 0.00 0.00 H ATOM 192 HI' GUA 258 0.200 3.543 0.476 0.00 0.00 H ATOM 193 HI GUA 258 1.736 1.057 5.844 0.00 0.00 H ATOM 194 1H2 GUA 258 3.175 0.274 2.790 0.00 0.00 H ATOM 195 2H2 GUA 258 3.025 -0.077 4.481 0.00 0.00 H ATOM 196 H8 GUA 258 -1.157 5.962 2.874 0.00 0.00 H ATOM 197 H2' GUA 258 -0.085 6.587 0.720 1.00 0.00 H ATOM 198 H02' GUA 258 -1.877 4.712 -0.384 0.00 0.00 H ATOM 199 H3' GUA 258 0.322 6.431 -1.760 0.00 0.00 H ATOM 200 P URA 259 -1.132 4.112 -2.710 0.00 67.33 P ATOM 201 OIP URA 259 -1.522 5.370 -3.385 0.00 67.46 O ATOM 202 02P URA 259 -2.136 3.451 -1.846 0.00 67.83 O ATOM 203 05' URA 259 -0.606 3.067 -3.771 0.00 67.75 O ATOM 204 C5' URA 259 0.003 3.536 -4.970 0.00 68.49 C ATOM 205 C4' URA 259 1.162 2.637 -5.420 0.00 69.20 C ATOM 206 04' URA 259 2.318 2.773 -4.540 0.00 69.18 O ATOM 207 Cl' URA 259 2.975 1.495 -4.423 0.00 69.15 C ATOM 208 Nl URA 259 2.968 0.994 -3.001 0.00 68.67 N ATOM 209 C6 URA 259 2.200 1.564 -1.978 0.00 68.48 C ATOM 210 C2 URA 259 3.862 -0.081 -2.699 0.00 68.09 C ATOM 211 02 URA 259 4.560 -0.665 -3.533 0.00 67.78 O ATOM 212 N3 URA 259 3.884 -0.461 -1.336 0.00 67.84 N ATOM 213 C4 URA 259 3.125 0.101 -0.280 0.00 68.39 C ATOM " 214 04 URA 259 3.220 -0.328 0.873 0.00 68.79 O ATOM 215 C5 URA 259 2.251 1.186 -0.685 0.00 68.73 c ATOM 216 C2' URA 259 2.257 0.570 -5.430 0.00 69.56 c ATOM 217 02' URA 259 2.834 0.684 -6.729 0.00 69.66 O ATOM 218 C3' URA 259 0.854 1.152 -5.371 0.00 69.75 c ATOM 219 03' URA 259 0.024 0.743 -6.457 0.00 71.19 0 ATOM 220 1H5' URA 259 0.387 4.580 -4.880 0.00 0.00 H ATOM 221 2H5' URA 259 -0.770 3.531 -5.770 0.00 0.00 H ATOM 222 H4' URA 259 1.502 2.943 -6.433 0.00 0.00 H ATOM 223 HI' URA 259 4.027 1.652 -4.746 0.00 0.00 H ATOM 224 H6 URA 259 1.535 2.360 -2.291 0.00 0.00 H ATOM 225 H3 URA 259 4.488 -1.234 -1.087 0.00 0.00 H ATOM 226 H5 URA 259 1.631 1.677 0.066 0.00 0.00 H ATOM 227 H2' URA 259 2.329 -0.473 -5.121 1.00 0.00 H ATOM 228 H02' URA 259 2.165 0.348 -7.330 0.00 0.00 H ATOM 229 H3' URA 259 0.418 0.897 -4.374 0.00 0.00 H ATOM 230 P ADE 260 -1.119 -0.326 -6.198 0.00 72.35 P ATOM 231 OIP ADE 260 -1.958 -0.423 -7.414 0.00 72.16 O ATOM 232 02P ADE 260 -1.802 -0.017 -4.922 0.00 71.24 O ATOM 233 05' ADE 260 -0.294 -1.667 -6.021 0.00 72.02 O ATOM 234 C5' ADE 260 0.334 -2.206 -7.183 0.00 72.26 C ATOM 235 C4' ADE 260 1.244 -3.391 -6.837 0.00 72.45 C ATOM 236 04' ADE 260 2.253 -3.015 -5.842 0.00 72.73 0 ATOM 237 Cl' ADE 260 2.381 -4.066 -4.871 0.00 72.84 c ATOM 238 C5 ADE 260 1.322 -3.560 -1.378 0.00 73.64 c ATOM 239 N7 ADE 260 0.980 -2.342 -1.894 0.00 73.11 N ATOM 240 C8 ADE 260 1.302 -2.426 -3.160 0.00 72.80 c ATOM 241 N9 ADE 260 1.865 -3.617 -3.537 0.00 73.10 N ATOM 242 Nl ADE 260 1.609 -5.338 0.119 0.00 74.80 N ATOM 243 C2 ADE 260 2.125 -6.026 -0.904 0.00 74.11 c ATOM 244 N3 ADE 260 2.312 -5.648 -2.170 0.00 73.90 N ATOM 245 C4 ADE 260 1.875 -4.380 -2.354 0.00 73.44 c ATOM 246 C6 ADE 260 1.184 -4.049 -0.066 0.00 74.18 c ATOM 247 N6 ADE 260 0.661 -3.243 0.906 0.00 74.42 N ATOM 248 C2' ADE 260 1.627 -5.267 -5.469 0.00 72.52 c ATOM 249 02' ADE 260 2.463 -5.994 -6.368 0.00 72.26 0 ATOM 250 C3' ADE 260 0.498 -4.544 -6.187 0.00 72.34 c ATOM 251 03' ADE 260 -0.160 -5.380 -7.138 0.00 72.21 0 ATOM 252 1H5' ADE 260 0.952 -1.432 -7.694 0.00 0.00 H ATOM 253 2H5' ADE 260 -0.443 -2.558 -7.901 0.00 0.00 H ATOM 254 H4* ADE 260 1.793 -3.733 -7.741 0.00 0.00 H ATOM 255 HI' ADE 260 3.463 -4.302 -4.783 0.00 0.00 H ATOM 256 H8 ADE 260 1.135 -1.655 -3.907 0.00 0.00 H ATOM 257 H2 ADE 260 2.440 -7.043 -0.670 0.00 0.00 H ATOM 258 1H6 ADE 260 0.366 -2.313 0.683 0.00 0.00 H ATOM 259 2H6 ADE 260 0.581 -3.580 1.847 0.00 0.00 H ATOM 260 H2' ADE 260 1.300 -5.949 -4.684 1.00 0.00 H ATOM 261 H02' ADE . 260 1.857 -6.467 -6.944 0.00 0.00 H ATOM 262 H3' ADE 260 -0.201 -4.133 -5.420 0.00 0.00 H ATOM 263 P GUA 261 ' -1.720 -5.641 -7.030 0.00 1.00 P ATOM 264 OIP GUA 261 -2.117 -6.583 -8.099 0.00 1.00 O ATOM 265 02P GUA 261 -2.424 -4.342 -6.968 0.00 1.00 O ATOM 266 05' GUA 261 -1.868 -6.360 -5.626 0.00 1.00 O ATOM 267 C5' GUA 261 -1.328 -7.667 -5.469 0.00 1.00 C ATOM 268 C4' GUA 261 -1.197 -8.050 -3.987 0.00 1.00 C ATOM 269 04' GUA 261 -0.450 -7.040 -3.235 0.00 1.00 O ATOM 270 Cl ' ' GUA 261 -1.072 -6.831 -1.959 0.00 1.00 C ATOM 271 N9 GUA 261 -1.638 -5.448 -1.872 0.00 1.00 N ATOM 272 C4 GUA 261 -2.178 -4.853 -0.715 0.00 1.00 C ATOM 273 N3 GUA 261 -2.283 -5.390 0.529 0.00 1.00 N ATOM 274 C2 GUA 261 -2.869 -4.570 1.446 0.00 1.00 C ATOM 275 Nl GUA 261 -3.297 -3.280 1.081 0.00 1.00 N ATOM 276 N2 GUA 261 -3.115 -4.866 2.753 0.00 1.00 N ATOM 277 C6 GUA 261 -3.195 -2.699 -0.211 0.00 1.00 C ATOM 278 06 GUA 261 -3.609 -1.566 -0.484 0.00 1.00 O ATOM 279 C5 GUA 261 -2.592 -3.579 -1.119 0.00 1.00 C ATOM 280 N7 GUA 261 -2.331 -3.378 -2.442 0.00 1.00 N ATOM- 281 C8 GUA 261 -1.776 -4.493 -2.841 0.00 1.00 C ATOM 282 C2' GUA 261 -2.108 -7.957 -1.819 0.00 1.00 C ATOM 283 02' GUA 261 -1.501 -9.131 -1.282 0.00 1.00 0 ATOM 284 C3' GUA 261 -2.532 -8.135 -3.270 0.00 1.00 C ATOM 285 03' GUA 261 -3.168 -9.389 -3.513 0.00 1.00 O ATOM 286 1H5' GUA 261 -0.316 -7.742 -5.932 0.00 0.00 H ATOM 287 2H5' GUA 261 -1.992 -8.406 -5.972 0.00 o.oo H ATOM 288 H4' GUA 261 -0.636 -9.004 -3.886 0.00 0.00 H ATOM 289 HI' GUA 261 -0.286 -6.948 -1.185 0.00 0.00 H ATOM 290 HI GUA 261 -3.739 -2.697 1.779 0.00 0.00 H ATOM 291 1H2 GUA 261 -2.849 -5.759 3.117 0.00 0.00 H ATOM 292 2H2 GUA 261 -3.570 -4.200 3.347 0.00 0.00 H ATOM 293 H8 GUA 261 -1.429 -4.707 -3.847 0.00 0.00 H ATOM 294 H2' GUA 261 -2.916 -7.652 -1.154 1.00 0.00 H ATOM ■ 295 H02-' GUA 261 -2.097 -9.847 -1.514 0.00 0.00 H x t^ o o o o z u o ^ u ^ o u o x x x x x x x x ^ x ai o o o a u o u ^ ^ ^ z ^ u o u z u u o u o si x x si r-- © CO O H U α. o o o o o o o o o o o o o o o o o o o o o o o o σ o o o o o o o o o o o o o o o o σ o o o o o o o o o o o o o o o o n cι T •» σ o o I I I I I I I I I -^ ιn (n ιΛ ιn (^J O o p^ fn ] ^D m ^ ^ ^ c ln σl c lΩ c^ ιn o f fJ N i -^ ιn ^l H H cη o l o H ^l co m lβ lfi ιη co σι co n τ M i CM •=!• -) ω ^ h ^ ι ιo ιn m ιn ιn « cιj H m ιo -) -i (n M ιfl ιn H θ m H H in ω m ιn cN -) θ ιn o ri (sι «) rn ιo <, -ι ιo n o H rH CO LD CM O CO CM r— -=T CO ^l ^ ω (^ H ri ln ι^ π H O O o m ^ Ol H eo H (ι « o π o -l H ^ « n ln ln m ω α) ^ ιη (^l Ol H ^ ■ !!l ^D l •) ^ι ^ r^ ^rninu)^. -^ r~ ^Γ o co n o n oo LD o in m co co CO CO n o O rH O LO ro r- en 00 σ rH en en ■=r LO LD r— r- co en en 1 1 1 1 rH rH rH rH 1 1 1 1 1 1 rH rH I I I I I I I i i 1 1 1 1 1 1 C r-~ co en o ιn o ro θ Lθ Lθ o cM ∞ cM θ ∞ cn o Lθ ,o ιn cD .-- cn cM cn cD cn cn ∞ o LD m co -o o c ^ co (^ -^ co co c C^ ^ r^ co o cri c CNj cn c r-- f LD r-- CD cD i c^ H ^ o ri ιη o ^ -' ^n ^ n fl ln c. ^ ln ω ^ ω ^ o ^ H O m o c^ -l ^ H O J - H <l' r' 7 f^ »l H ", o m ιn (ι t^ ω α) (Il O H H ln (^ι ^ Ol co -cf m m -n -o -n -sf -n m -O D O LD LD o -n O LD LD ^ in in -. m r- r— cn -n co o o o -n o en en ΓH J i l l I cc p-l p-l p-l e-i P-; p-| r--, c-; „ I-3 C. D D D D D -D D D ( „ C-Di β ; D, K ff; ^ ^ -, l-i l-i ^ rt i l-i ^ C, (-; D D D D D D D D D D P --J D 3 D D D D D D D D !-) D D D D D D D D D D S D D D D D D D D U U O -l -l -ι - ) -l ϋ U U U -ι -) U a L5 U -I O O -l -l ) -l -l l. CJ S O S Z O O ϋ sc o o o a o o u o o a o c ca cc C EC O EC O O O CJ U O O O O O O C EC 3-; rH CM - l ω m o ri c^ι n ^ ln ω ^ ∞ ffi O ri N π ^ ln ιo ^ ω m o H N ιη ^ fl - ι ^ ω m o ri N n « ι -' ^ co ^ o ri rι t r l « ln ιo r- o ol O ri N f^ cn C Cn cn o O O O O CD O O O O rH rH rH rH rH rH i-H rH rH rH CM CM CM CM CM CM CM CM CM CM CO C^ CO CO CO CO O C^ cM CM CM CM co co co ^ co co ro co co co co ro co co m ro co co ro co co co co co ro c^ o O 2o2o2o2oo22o2o2o2o2o2o2o 2o2o2o2oSoo22o2o2oSo2o2o2o2o2o2o2o2ooS 2o2o2oo2o22ooSo22oo2 ATOM 356 2H2 GUA 263 -12.035 -0.727 2.492 0.00 0.00 H ATOM 357 H8 GUA 263 -9.583 -7.493 0.275 0.00 0.00 H ATOM 358 H2' GUA 263 -12.608 -6.540 3.022 1.00 0.00 H ATOM 359 H02' GUA 263 -12.887 -7.954 4.861 0.00 0.00 H ATOM 360 H3' GUA 263 -12.197 -8.401 1.477 0.00 0.00 H ATOM 361 P URA 264 -14.436 -9.796 2.163 0.00 0.00 P ATOM 362 OIP URA 264 -15.096 ■ -10.985 2.747 0.00 0.00 O ATOM 363 02P URA 264 -14.023 -9.877 0.744 0.00 0.00 O ATOM 364 05' URA 264 -15.387 -8.544 2.344 0.00 0.00 O ATOM 365 C5' URA 264 -15.980 -8.298 3.617 0.00 0.00 c ATOM 366 C4' URA 264 -16.173 -6.795 3.880 0.00 0.00 c ATOM 367 04 ' URA 264 -14.917 -6.065 3.724 0.00 0.00 O ATOM 368 Cl' URA 264 -15.167 -4.801 3.092 0.00 0.00 c ATOM 369 Nl URA 264 -14.517 -4.680 1.741 0.00 0.00 N ATOM 370 C6 URA 264 -14.072 -5.757 0.965 0.00 0.00 C ATOM 371 C2 URA 264 -14.514 -3.366 1.193 0.00 0.00 C ATOM 372 02 URA 264 -14.890 -2.362 1.806 0.00 0.00 0 ATOM 373 N3 URA 264 -14.043 -3.282 -0.137 0.00 0.00 N ATOM 374 C4 URA 264 -13.556 -4.344 -0.940 0.00 0.00 C ATOM 375 04 URA 264 -13.141 -4.141 -2.085 0.00 0.00 O ATOM 376 C5 URA 264 -13.596 -5.644 -0.293 0.00 0.00 C ATOM 377 C2' URA 264 -16.699 -4.658 3.044 0.00 0.00 C ATOM 378 02' URA 264 -17.172 -4.067 4.253 0.00 0.00 O ATOM 379 C3' URA 264 -17.114 -6.116 2.900 0.00 0.00 C ATOM 380 03' URA 264 -18.481 -6.357 3.231 0.00 0.00 O ATOM 381 1H5' URA 264 -15.363 -8.710 4.451 0.00 0.00 H ATOM 382 2H5' URA 264 -16.973 -8.798 3.654 0.00 0.00 H ATOM 383 H4' URA 264 -16.513 -6.632 4.926 0.00 0.00 H ATOM 384 HI' URA 264 -14.733 -4.033 3.769 0.00 0.00 H ATOM 385 H6 URA 264 -14.118 -6.726 1.442 0.00 0.00 H ATOM 386 H3 URA 264 -14.053 -2.356 -0.541 0.00 0.00 H ATOM 387 H5 URA 264 -13.240 -6.521 -0.835 0.00 0.00 H ATOM 388 H2' URA 264 -16.988 -4.026 2.204 1.00 0.00 H ATOM 389 H02' URA 264 -18.130 -4.091 4.183 0.00 0.00 H ATOM 390 H3' URA 264 -16.869 -6.467 1.869 0.00 0.00 H ATOM 391 P URA 265 -19.593 -6.111 2.126 0.00 46.64 P ATOM 392 OIP URA 265 -19.066 -6.504 0.800 0.00 32.38 O ATOM 393 02P URA 265 -20.847 -6.755 2.575 0.00 56.93 O ATOM 394 05' URA 265 -19.770 -4.535 2.152 0.00 26.86 O ATOM 395 C5' URA 265 -20.462 -3.956 3.256 0.00 35.20 C ATOM 396 C4 ' URA 265 -20.757 -2.466 3.027 0.00 45.98 C ATOM 397 04' ITRA 265 -19.543 -1.689 2.791 0.00 50.88 O ATOM 398 Cl' URA 265 -19.857 -0.589 1.912 0.00 45.26 C ATOM 399 Nl URA 265 -18.953 -0.579 0.710 0.00 38.99 N ATOM 400 C6 URA 265 -18.500 -1.748 0.089 0.00 23.80 C ATOM 401 C2 URA 265 -18.706 0.693 0.098 0.00 29.79 C ATOM 402 02 URA 265 -19.101 1.771 0.554 0.00 31.88 O ATOM 403 N3 URA 265 -17.965 0.634 -1.112 0.00 17.61 N ATOM 404 C4 URA 265 -17.481 -0.535 -1.754 0.00 31.42 C ATOM 405 04 URA 265 -16.851 -0.474 -2.815 0.00 23.03 0 ATOM 406 C5 URA 265 -17.795 -1.773 -1.061 0.00 28.82 c ATOM 407 C2' URA 265 -21.364 -0.726 1.575 0.00 40.06 c ATOM 408 02' URA 265 -22.145 0.058 2.478 0.00 44.52 0 ATOM 409 C3' URA 265 -21.574 -2.221 1.778 0.00 39.85 c ATOM 410 03' URA 265 -22.942 -2.588 1.965 0.00 48.03 0 ATOM 411 1H5' URA 265 -19.859 -4.065 4.184 0.00 0.00 H ATOM 412 2H5' URA 265 -21.438 -4.469 3.420 0.00 0.00 H ATOM 413 H4' URA 265 -21.254 -2.031 3.922 0.00 0.00 H ATOM 414 HI' URA 265 -19.688 0.331 2.514 0.00 0.00 H ATOM 415 H6 URA 265 -18.762 -2.674 0.597 0.00 0.00 H ATOM 416 H3 URA 265 -17.790 1.511 -1.590 0.00 0.00 H ATOM 417 H5 URA 265 -17.466 -2.718 -1.494 0.00 0.00 H ATOM 418 H2' URA 265 -21.555 -0.383 0.558 1.00 0.00 H ATOM 419 H02' URA 265 -22.123 0.959 2.137 0.00 0.00 H ATOM 420 H3' URA 265 •■ -21.098 -2.757 0.919 0.00 0.00 H ATOM 421 P GUA 266 -23.694 -3.346 0.799 0.00 43.63 P ATOM 422 OIP GUA 266 -22.890 . -4.508 0.358 0.00 36.61 O ATOM 423 02P GUA 266 -25.092 -3.596 1.214 0.00 64.56 O ATOM 424 05' GUA 266 -23.697 -2.251 -0.341 0.00 28.91 O ATOM 425 C5' GUA 266 -24.077 -2.659 -1.652 0.00 29.01 C ATOM 426 C4' GUA 266 -24.651 -1.486 -2.453 0.00 27.64 C ATOM 427 04' GUA 266 -25.859 -0.957 -1.818 0.00 38.10 O ATOM 428 Cl 1 GUA 266 -25.820 0.477 -1.836 0.00 27.61 C ATOM 429 9 GUA 266 -25.655 1.004 -0.444 0.00 0.00 N ATOM 430 C4 GUA 266 -25.675 2.363 -0.078 0.00 0.00 C ATOM 431 N3 GUA 266 -25.788 3.444 -0.894 0.00 0.00 N ATOM 432 C2 GUA 266 -25.772 4.641 -0.245 0.00 0.00 C ATOM 433 Nl GUA 266 -25.663 4.694 1.157 0.00 0.00 N ATOM 434 N2 GUA 266 -25.850 5.872 -0.826 0.00 0.00 N ATOM 435 C6 GUA 266 -25.550 3.577 2.030 0.00 0.00 C ATOM 436 06 GUA 266 -25.460 3.682 3.258 0.00 0.00 O ATOM 437 C5 GUA 266 -25.559 2.369 1.316 0.00 0.00 C ATOM 438 N7 GUA 266 -25.468 1.097 1.804 0.00 0.00 N ATOM 439 C8 GUA 266 -25.529 0.331 0.743 0.00 0.00 C ATOM 440 C2' GUA 266 -24.674 0.849 -2.798 0.00 37.08 C ATOM 441 02' GUA 266 -25.132 0.863 -4.149 0.00 37.59 0 ATOM 442 C3' GUA 266 -23.709 -0.295 -2.526 0.00 32.19 c ATOM 443 03' GUA 266 -22.735 -0.459 -3.558 0.00 40.82 0 ATOM 444 1H5' GUA 266 -24.841 -3.474 -1.634 0.00 0.00 H ATOM 445 2H5' GUA 266 -23.177 -3.045 -2.181 0.00 0.00 H ATOM 446 H4' GUA 266 -24.948 -1.821 -3.471 0.00 0.00 H ATOM 447 HI' GUA 266 -26.792 0.827 -2.244 0.00 0.00 H ATOM 448 HI GUA 266 -25.658 5.595 1.610 0.00 0.00 H ATOM 449 1H2 GUA 266 -25.820 6.700 -0.267 0.00 0.00 H ATOM 450 2H2 GUA 266 -25.925 5.942 -1.821 0.00 0.00 H ATOM 451 H8 GUA 266 -25.516 -0.758 0.740 0.00 0.00 H ATOM 452 H2' GUA 266 -24.278 1.837 -2.564 1.00 0.00 H ATOM 453 H02' GUA 266 -24.339 0.758 -4.682 0.00 0.00 H ATOM 454 H3' GUA 266 -23.249 -0.121 -1.523 0.00 0.00 H ATOM 455 P GUA 267 -21.201 -0.212 -3.250 0.00 34.70 P ATOM 456 OIP GUA 267 -20.859 -0.840 -1.956 0.00 37.33 O ATOM 457 02P GUA 267 -20.407 -0.611 -4.432 0.00 24.34 0 ATOM 458 05' GUA 267 -21.140 1.363 -3.088 0.00 20.77 0 ATOM 459 C5' GUA 267 -21.313 2.160 -4.258 0.00 19.81 0 ATOM 460 C4' GUA 267 -21.532 3.641 -3.914 0.00 22.36 c ATOM 461 04' GUA 267 -22.706 3.830 -3.064 0.00 23.18 0 ATOM 462 Cl' GUA 267 -22.414 4.811 -2.057 0.00 23.36 c ATOM 463 N9 GUA 267 -22.411 4.174 -0.706 0.00 0.00 N ATOM 464 C4 GUA 267 -22.411 4.864 0.519 0.00 ' 0.00 c ATOM 465 N3 GUA 267 -22.496 6.206 0.718 0.00 0.00 N ATOM 466 C2 GUA 267 -22.487 6.578 2.029 0.00 0.00 C ATOM 467 Nl GUA 267 -22.387 5.610 3.047 0.00 0.00 N ATOM 468 N2 GUA 267 -22.570 7.853 2.503 0.00 0.00 N ATOM 469 C6 GUA 267 -22.288 4.204 2.859 0.00 0.00 C ATOM 470 06 GUA 267 -22.188 3.396 3.790 0.00 0.00 O ATOM 471 C5 GUA 267 -22.315 3.872 1.498 0.00 0.00 C ATOM 472 N7 GUA 267 -22.263 2.633 0.932 0.00 0.00 N ATOM 473 C8 GUA 267 -22.327 2.855 -0.354 0.00 0.00 C ATOM 474 C2' GUA 267 -21.060 5.439 -2.453 0.00 26.79 C ATOM 475 02 ' GUA 267 -21.253 6.517 -3.367 0.00 29.84 O ATOM 476 C3' GUA 267 -20.394 4.239 -3.109 0.00 23.44 C ATOM 477 03' GUA 267 -19. 298 4.595 -3.954 0.00 37.12 0 ATOM 478 1H5' GUA 267 -22. 186 1.811 -4.857 0.00 0.00 H ATOM 479 2H5' GUA 267 -20. 403 2.079 -4.895 0.00 0.00 H ATOM 480 H4' GUA 267 -21. 712 4.227 -4.842 0.00 0.00 H ATOM 481 . HI' GUA 267 -23. 220 5.575 -2.102 0.00 0.00 H ATOM 482 HI GUA 267 -22. 377 5.914 4.009 0.00 0.00 H ATOM . 483 1H2 GUA 267 -22. 553 8.031 3.486 0.00 0,00 H ATOM 484 2H2 GUA 267 -22. ,639 8.615 1.858 0.00 0.00 H ATOM 485 H8 GUA 267 -22. 337 2.095 -1.129 0.00 0.00 H ATOM 486 H2' GUA 267 -20. 543 5.825 -1.574 1.00 0.00 H ATOM 487 H02' GUA 267 -20. ,403 6.630 -3.801 0.00 0.00 H ATOM 488 H3' GUA 267 -20. ,110 ' 3.522 -2.297 0.00 0.00 H ATOM 489 P GUA 268 -17. 843 4.185 -3.493 0.00 0.00 P ATOM 490 OIP GUA 268 -17. ,367 5.158 -2.484 0.00 0.00 0 ATOM 491 02P GUA 268 -17. ,835 2.757 -3.110 0.00 0.00 0 ATOM 492 05' GUA 268 -17. .020 4.349 -4.830 0.00 0.00 0 ATOM 493 C5' GUA 268 -16. .480 5.604 -5.227 0.00 0.00 C ATOM 494 C4' GUA 268 -14. ,953 5.568 -5.469 0.00 0.00 C ATOM 495 04' GUA 268 -14. ,236 5.111 -4.281 0.00 0.00 0 ATOM 496 Cl' GUA 268 -13. ,691 3.802 -4.501 0.00 0.00 C ATOM 497 N9 GUA 268 -13. .989 2.950 -3.307 0.00 0.00 N ATOM 498 C4 GUA 268 -13. .625 1.602 -3.122 0.00 0.00 C ATOM 499 N3 GUA 268 -12. .884 0.810 -3.944 0.00 0.00 N ATOM 500 C2 GUA 268 -12. .708 -0.463 -3.492 0.00 0.00 C ATOM 501 Nl GUA 268 -13. .257 -0.863 -2.262 0.00 0.00 N ATOM 502 N2 GUA 268 -12, .019 -1.457 -4.119 0.00 0.00 N ATOM 503 C6 GUA 268 -14, .022 -0.046 -1.384 0.00 0.00 C ATOM 504 06 GUA 268 -14, .475 -0.436 -0.304 0.00 0.00 0 ATOM 505 C5 GUA 268 -14, .184 1.243 -1.894 0.00 0.00 c ATOM 506 N7 GUA 268 -14, .851 2.288 -1.329 0.00 0.00 N ATOM 507 C8 GUA 268 -14, .700 3.268 -2.180 0.00 0.00 c ATOM 508 C2' GUA 268 -14, .305 3.307 -5.834 0.00 0.00 c ATOM 509 02' GUA 268 -13, .476 2.386 -6.538 0.00 0.00 0 ATOM 510 C3' GUA 268 -14 .513 4.620 -6.583 0.00 0.00 c ATOM 511 03' GUA 268 -13 .283 5.034 -7.184 0.00 0.00 0 ATOM 512 1H5' GUA 268 -16 .690 6.412 -4.486 0.00 0.00 H ATOM 513 2H5' GUA 268 -16, .972 5.909 -6.176 0.00 0.00 H ATOM 514 H4' GUA 268 -14 .633 6.609 -5.666 0.00 0.00 H ATOM 515 ' HI' GUA 268 -12 .595 3.944 -4.618 0.00 0.00 H ATOM 516 HI GUA 268 ' -13 .094 -1.811 -1.957 0.00 0.00 H ATOM 517 1H2 GUA 268 -11 .590 -1.280 -5.004 0.00 0.00 H ATOM 518 2H2 GUA 268 -11 .940 -2.362 -3.698 0.00 0.00 H ATOM 519 H8 GUA 268 -15 .068 4.286 -2.051 0.00 0.00 H ATOM 520 H2' GUA 268 -15 .258 2.792 -5.712 1.00 0.00 H ATOM 521 H02' GUA 268 -12 .767 2.922 -6.902 0.00 0.00 H ATOM ' 522 H3' GUA 268 -15 .306 4.504 -7.355 0.00 0;00 H ATOM 523 P URA 269 -13 .215 6.295 -8.134 0.00 0.00 P ATOM 524 OIP URA 269 -12 .172 6.068 -9.159 0.00 0.00 0 ATOM 525 02P URA 269 -14 .573 6.645 -8.608 0.00 0.00 0 ATOM 526 05' URA 269 -12 .727 7.413 -7.127 0.00 0.00 0 ATOM 527 C5' URA 269 -11 .360 7.412 -6.723 0.00 0.00 c ATOM 528 C4' URA 269 -11 .073 8.410 -5.581 0.00 0.00 c ATOM 529 04' URA 269 -11 .585 9.744 -5.914 0.00 0.00 0 ATOM 530 Cl' URA 269 -12 .555 10.145 -4.941 0.00 0.00 c ATOM 531 Nl URA 269 -13 .643 10.948 -5.588 0.00 0.00 N ATOM 532 C6 URA 269 -14 .300 10.505 -6.738 0.00 0.00 c ATOM 533 C2 URA 269 -14 .147 12.074 -4.866 0.00 0.00 c ATOM 534 02 URA 269 -13 .640 12.522 -3.833 0.00 0.00 0 ATOM 535 N3 URA 269 -15 .314 12.658 -5.425 0.00 0.00 N ι-β H ι-- H H H H H .-3 ι-- H ι-6 H ι-- H '-- H ι-- ι-- H H ^ H >-- H ι-- ι-3 H >-3 ι-- i-- ι-- ι-- H o o o o o o o o o o o o o o o o o o o o o o o o o o o o o oo o o o o o o o o o o o o o o o o o o o o o o o o o o o o o 222222222 S 222222222222 S 22 -<: 22222222 S 22 :--; 22232 S 3: 2322 :--: 2222222222 (-π c_n -Ji -7i C-π uι cπ U^ -7i (-π oπ (-π c-π αι U (_π Ji -i (-π Uι ι cn LO LD LO LO LO LO CO -O CX ) -O CO CO CO CO CO CO --J -- ] --J --J --- --J — ! ^ >J ) m C^ C^ ^ CΛ m C σι Φ -l Ul Ul Ln Ul !Jl -l Ul Ul Ul -> Λ ,- -i -ι -> J- J- - i -. -] ι) -J U EC M C O O O O O O EC O EC M r H EC EC EC EC O O O O O O O O O O O EC O EC O Z O -2 r-i J-. EC EC EC O O O O *> u i u i μ ui ro c tc a EC ^ -n ( -n - A j . . n --I o s-. O Q O μ *. *. Ui Ui μ GJ to ro EC EC EC ro ω J-> LO - - - - - r , ι-i rrj - - - π t. ^ σi - - - - - - - - ui j M fo σi >fl i . ι- - - - -ι ω m n o o Q no n n o o o o o n o o o o o o o o o o o o o o o no o o o o o oo o o o o o G G G G G G G G G G G G G G G G G G G G G G G G G G G G H^ I^ I^ I-^ ^ W W W W SO ggg I I I J I I I I I I I I I I I I I -> μ j μ-> CO LO LD LO LO LO CO CO OO CO O rO H-" O LD LD H-" U) P o r O O J jJ Ln -- en e θ CO OT LD μ J -J ) μ μ μ μ M ω o o H *. σi ui ω I I I I I I I I I I I I I il- J- 00 ro j-. co α- * - j »--. c-π -n ---ι θϋ »t-. (--> --> en en - j co μ j cπ ro μ- 1 -J Λ c j -» w ) -> -ι j- o cD θ ra ω o o o o o o o o o o σ o o o o o o o σ o o o o o o o o o o o o o o o o o o o o o o o cD O O o o o o o o o o o o o σ o σ o o o o o o o σ σ o o o o σ o o o o o o o o o o o o o o o o o o o o o o σ o o o o o o o σ σ o o o σ o σ σ o o o o o eD O CD μj o eD CD CD o c O O o o o o o o o o o o o o -D o o o o o o o o o σ o o o o o σ σ o o σ o o o o o o O O O O O O O O O O O O O O O O O O O O O O O O CD O CD O CD O CD O O O O CD O O O CD O CD CD O CD O O O CD O CD O CD O CD O CD O O CD o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o σ o o o o o o o o o o o o o o o o o zn z π o n no o o '. ϊ K ϊ ϊ ϊ t - K ϊ ϊ ϊ ϊ O O o no z o z o n n a n o n o o o o . ϊ a ϊ ϊ E ffi a ϊ a ϊ o n o n n o n ATOM 596 Nl GUA 271 -8.186 -2.378 2.894 0.00 1.00 N ATOM 597 N2 GUA 271 -8.609 -3.509 4.865 0.00 1.00 N ATOM 598 C6 GUA 271 -8.128 -1.297 1.973 0.00 1.00 c ATOM 599 06 GUA 271 -7.719 -1.405 0.813 0.00 1.00 0 ATOM 600 C5 GUA 271 -8.604 -0.113 2.543 0.00 1.00 c ATOM 601 N7 GUA 271 -8.655 1.127 1.981 0.00 1.00 N ATOM 602 C8 GUA 271 -9.167 1.887 2.912 0.00 1.00 c ATOM 603 C2' GUA. 271 -9.082 1.826- 6.510 0.00 1.00 c ATOM 604 02' GUA 271 -9.763 1.731 7.760 0.00 1.00 0 ATOM 605 C3' GUA 271 -8.465 , 3.200 6.287 0.00 1.00 c ATOM 606 03' GUA 271 -7.781 3.674 7.447 0.00 1.00 0 ATOM 607 1H5' GUA 271 -10.353 5.918 5.150 0.00 0.00 H ATOM 608 2H5' GUA 271 -8.667 5.924 5.787 0.00 0.00 H ATOM 609 H4' GUA 271 -10.270 4.253 6.889 0.00 0.00 H ATOM 610 HI' GUA 271 -10.965 1.160 5.615 0.00 0.00 H ATOM 611 HI GUA 271 -7.839 -3.263 2.552 0.00 0.00 H ATOM 612 1H2 GUA 271 -8.229 -4.314 4.409 0.00 0.00 H ATOM 613 2H2 GUA 271 -8.934 -3.576 5.808 0.00 0.00 H ATOM 614 H8 GUA 271 -9.325 2.957 2.836 0.00 0.00 H ATOM 615 H2' GUA 271 -8.370 1.003 6.448 1.00 0.00 H ATOM 616 H02' GUA 271 -9.151 2.095 8.405 0.00 0.00 H ATOM 617 H3' GUA 271 -7.805 3.158 . 5.386 0.00 0.00 H ATOM 618 P CYT 272 -6.201 3.803 7.461 0.00 1.00 P ATOM 619 OIP CYT 272 -5.796 4.449 8.729 0.00 1.00 O ATOM 620 02P CYT 272 -5.762 4.443 6.201 0.00 1.00 O ATOM 621 05' CYT 272 -5.701 2.298 7.467 0.00 1.00 O ATOM 622 C5' CYT 272 -5.871 1.513 8.644 0.00 1.00 c ATOM 623 C4' CYT 272 -5.693 0.008 8.369 0.00 i.oo ■ C ATOM 624 04' CYT 272 -6.571 -0.445 7.285 0.00 1.00 0 ATOM 625 Cl' CYT 272 -5.858 -1.343 6.417 0.00 1.00 C ATOM 626 Nl CYT 272 -5.638 -0.776 5.035 0.00 1.00 N ATOM 627 C6 CYT 272 -5.895 0.544 4.677 0.00 1.00 c ATOM 628 C2 CYT 272 -5.128 -1.673 4.033 0.00 1.00 c ATOM 629 02 CYT 272 -4.914 -2.875 4.283 0.00 1.00 0 ATOM 630 N3 CYT 272 -4.901 -1.182 2.764 0.00 1.00 N ATOM 631 C4 CYT 272 -5.174 0.108 2.437 0.00 1.00 C ATOM 632 N4 CYT 272 -5.010 0.574 1.166 0.00 1.00 N ATOM 633 C5 CYT 272 -5.675 1.014 3.440 0.00 1.00 C ATOM 634 C2' CYT 272 -4.563 -1.682 7.172 0.00 1.00 C ATOM • 635 02' CYT- 272 -4.779 -2.771 8.068 0.00 1.00 O ATOM 636 C3' CYT 272 -4.296 -0.374 7.903 0.00 1.00 C ATOM 637 03' CYT 272 -3.389 -0.559 8.990 0.00 1.00 O ATOM 638 1H5' CYT 272 -6.887 1.665 9.076 0.00 0.00 H ATOM 639 2H5' CYT 272 -5.122 1.825 9.406 0.00 0.00 H ATOM 640 H4' CYT 272 -5.974 -0.577 9.271 0.00 0.00 H ATOM 641 HI' CYT 272 -6.492 -2.253 6.330 0.00 0.00 H ATOM 642 H6 CYT 272 -6.341 1.175 5.435 0.00 0.00 H ATOM 643 1H4 CYT 272 -5.231 1.525 0.948 0.00 0.00 H ATOM 644 2H4 CYT 272 -4.673 -0.041 0.451 0.00 0.00 H ATOM 645 H5 CYT 272 -5.903 2.048 3.176 0.00 0.00 H ATOM 646 H2' CYT 272 -3.776 -1.962 6.472 1.00 0.00 H ATOM 647 H02' CYT 272 -4.108 -2.670 8.748 0.00 0.00 H ATOM 648 H3' CYT 272 -3.939 0.387 7.167 0.00 0.00 H ATOM 649 P GUA 273 -1.928 0.046 8.936 0.00 65.10 P ATOM 650 OIP GUA 273 -1.210 -0.342 10.170 0.00 64.77 O ATOM 651 02P GUA 273 -2.025 1.489 8.630 0.00 64.57 O ATOM 652 05' GUA 273 -1.262 -0.692 7.701 0.00 64.14 O ATOM 653 C5' GUA 273 -0.960 -2.080 7.786 0.00 62.38 C ATOM 654 C4' GUA 273 -0.565 -2.667 6.417 0.00 61.99 C ATOM 655 04' GUA 273 -1.601 -2.439 5.408 0.00 61.34 O ATOM 656 Cl' GUA 273 -1.003 -2.017 4.173 0.00 60.75 C ATOM 657 N9 GUA 273 -1.420 -0.611 3.858 0.00 60.16 N ATOM 658 C4 GUA 273 -1.406 0.000 2.584 0.00 59.63 c ATOM 659 N3 GUA 273 -0.928 -0.505 1.413 0.00 58.77 N ATOM 660 C2 GUA 273 -1.126 0.308 0.331 0.00 58.33 c ATOM 661 Nl GUA 273 -1.742 1.563 0.483 0.00 58.87 N ATOM 662 N2 GUA 273 -0.800 0.040 -0.965 0.00 57.26 N ATOM 663 C6 -GUA 273 -2.236 2.111 1.696 0.00 59.39 c ATOM 664 06 GUA 273 -2.813 3.202 1.768 0.00 60.03 0 ATOM 665 C5 GUA 273 -2.033 1.238 2.770 0.00 59.49 c ATOM 666 N7 GUA 273 -2.403 1.411 4.068 0.00 59.69 N ATOM 667 C8 GUA 273 -2.038 0.308 4.663 0.00 59.91 c ATOM 668 C2' GUA 273 0.513 -2.257 4.340 0.00 61.01 c ATOM 669 02' GUA 273 0.845 -3.592 3.960 0.00 60.10 0 ATOM 670 C3' GUA 273 0.685 -2.026 5.839 0.00 61.69 c ATOM 671 03' GUA 273 1.848 -2.637 6.399 0.00 62.51 0 ATOM 672 1H5' GUA 273 -1.837 -2.650 8.170 0.00 0.00 H ATOM 673 2H5' GUA 273 -0.114 -2.232 8.494 0.00 0.00 H ATOM 674 H4' GUA 273 -0.440 -3.769 6.496 0.00 0.00 H ATOM 675 HI' GUA 273 -1.404 -2.686 3.382 0.00 0.00 H ATOM 676 HI GUA 273 -1.894 2.134 -0.339 0.00 0.00 H ATOM 677 1H2 GUA 273 -0.375 -0.836 -1.204 0.00 0.00 H ATOM 678 2H2 GUA 273 -1.024 0.694 -1.689 0.00 0.00 H ATOM 679 H8 GUA 273 -2.246 0.059 5.696 0.00 0.00 H ATOM 680 H2' GUA 273 1.075 -1.564 3.713 1.00 0.00 H ATOM 681 H02' GUA 273 1.751 -3.726 4.256 0.00 0.00 H ATOM 682 H3' GUA 273 0.652 -0.929 6.039 0.00 0.00 H ATOM 683 P ADE 274 3.219 -1.854 6.459 0.00 63.35 P ATOM 684 OIP ADE 274 4.117 -2.542 7.413 0.00 62.97 O ATOM 685 02P ADE 274 2.961 -0.413 6.679 0.00 63.64 O ATOM 686 05' ADE 274 3.751 -2.043 4.986 0.00 64.75 0 ATOM 687 C5' ADE 274 5.004 -2.654 4.715 0.00 66.11 c ATOM 688 C4' ADE 274 4.886 -4.169 4.519 0.00 67.14 c ATOM 689 04' ADE 274 3.850 -4.490 3.532 0.00 68.13 0 ATOM 690 Cl' ADE 274 4.373 -5.422 2.575 0.00 68.71 c ATOM 691 C5 ADE 274 5.104 -4.329 -0.862 0.00 68.97 c ATOM 692 N7 ADE 274 4.802 -3.122 -0.301 0.00 69.49 N ATOM 693 C8 ADE 274 4.518 -3.403 0.947 0.00 69.25 C ATOM 694 N9 ADE 274 4.624 -4.729 1.273 0.00 69.39 N ATOM 695 Nl ADE 274 5.706 -5.967 -2.427 0.00 69.25 N ATOM 696 C2 ADE 274 5.587 -6.857 -1.438 0.00 69.22 C ATOM 697 N3 ADE 274 5.252 -6.666 -0.158 0.00 68.91 N ATOM 698 C4 ADE 274 5.018 -5.351 0.075 0.00 69.25 C ATOM 699 C6 ADE 274 5.466 -4.638 -2.188 0.00 68.74 C ATOM 700 N6 ADE 274 5.549 -3.640 -3.120 0.00 68.24 N ATOM 701 C2' ADE 274 5.643 -5.994 3.224 0.00 68.48 C ATOM 702 02' ADE 274 5.329 -7.028 4.155 0.00 69.65 0 ATOM 703 C3' ADE 274 6.159 -4.738 3.906 0.00 67.76 c ATOM 704 03' ADE 274 7.173 -5.009 4.874 0.00 67.35 0 ATOM 705 1H5' ADE 274 5.754 -2.436 5.510 0.00 0.00 H ATOM 706 2H5' ADE 274 5.397 -2.208 3.778 0.00 0.00 H ATOM 707 H4' ADE 274 4.616 -4.684 5.464 0.00 0.00 H ATOM 708 HI' ADE 274 3.612 -6.219 2.434 0.00 0.00 H ATOM 709 H8 ADE 274 4.209 -2.689 1.710 0.00 0.00 H ATOM 710 H2 ADE 274 5.798 -7.890 -1.715 0.00 0.00 H ATOM 711 1H6 ADE 274 5.350 -2.694 -2.862 0.00 0.00 H ATOM 712 2H6 ADE 274 5.815 -3.858 -4.058 0.00 0.00 H ATOM 713 H2' ADE 274 6.314 -6.417 2.476 1.00 0.00 H ATOM 714 H02' ADE 274 6.083 -7.066 4.749 0.00 0.00 H ATOM 715 H3' ADE 274 6.507 -4.035 3.109 0.00 0.00 H ATOM 716 P ADE 275 8.663 -4.528 4.605 0.00 67.69 P ATOM 717 OIP ADE 275 9. 472 -4. 777 5.818 0.00 67.60 0 ATOM 718 02P ADE 275 8. 637 -3. 147 4.071 0.00 67.94 0 ATOM 719 05' ADE 275 9. 155 -5. 495 3.449 0.00 67.85 0 ATOM 720 C5' ADE 275 9. 357 -6. 871 3.752 0.00 67.53 c ATOM 721 C4' ADE 275 9. 470 -7. 730 2.481 0.00 67.23 c ATOM 722 04' ADE 275 8. 323 -7. 528 1.592 0.00 67.09 0 ATOM 723 Cl' ADE 275 8. 780 -7. 452 0.234 0.00 66.99 c ATOM 724 C5 ADE 275 8. 672 -4. 281 -1.636 0.00 67.99 c ATOM 725 N7 ADE 275 8. 327 -3. 821 -0.397 0.00 67.87 N ATOM 726 C8 ADE 275 8. 304 -4. 895 0.352 0.00 67.37 c ATOM 727 N9 ADE 275 8. 639 -6. 057 -0.294 0.00 67.47 N ATOM 728 Nl ADE 275 9. 128 -4. 354 -3.934 0.00 67.93 N ATOM 729 C2 ADE 275 9. 292 -5. 673 -3.790 0.00 68.10 c ATOM 730 N3 ADE 275 9. ,199 -6. 425 -2.690 0.00 67.88 N ATOM 731 C4 ADE 275 8. 871 -5. 657 -1.622 0.00 67.85 c ATOM 732 C6 ADE 275 8. 819 -3. 577 -2.846 0.00 67.86 c ATOM 733 N6 ADE 275 8. 651 -2. 218 -2.863 0.00 68.36 N ATOM 734 C2' ADE 275 10. ,233 -7. 953 0.269 0.00 66.60 c ATOM 735 02' ADE 275 10. ,280 -9. 378 0.228 0.00 66.18 0 ATOM 736 C3' ADE 275 10. .673 -7. 392 1.615 0.00 66.74 c ATOM 737 03' ADE 275 11. ,864 -7. 995 2.117 0.00 66.98 0 ATOM 738 1H5' ADE 275 8. .514 -7. 273 4.361 0.00 0.00 H ATOM 739 2H5' ADE 275 10. .293 -6. 987 4.343 0.00 0.00 H ATOM 740 H4' ADE 275 9, .477 -8. ,808 2.754 0.00 0.00 H ATOM 741 HI' ADE 275 8. .147 -8. ,139 -0.368 0.00 0. 00 H ATOM 742 H8 ADE 275 8. .001 -4. ,935 1.393 0.00 0.00 H ATOM 743 H2 ADE 275 9, .549 -6. ,212 -4.702 0.00 0.00 H ATOM 744 1H6 ADE 275 8, .421 -1. ,737 -2.016 0.00 0.00 H ATOM 745 2H6 ADE 275 8, .759 -1. .713 -3.718 0.00 0.00 H ATOM 746 H2' ADE 275 10, .796 -7. .572 -0.583 1.00 0.00 H ATOM 747 H02' ADE 275 11 .185 -9. .606 0.454 0.00 0.00 H ATOM 748 H3' ADE 275 10 .758 -6, .282 1.534 0.00 0.00 H ATOM 749 P ADE 276 13 .260 -7, .257 1.977 0.00 65.98 P ATOM 750 OIP ADE 276 14 .232 -7, .912 2.879 0.00 66.78 O ATOM 751 02P ADE 276 13 .062 -5, .798 2.130 0.00 66.40 O ATOM 752 05' ADE 276 13 .667 -7, .554 0.476 0.00 67.08 0 ATOM 753 C5' ADE 276 13 .989 -8. .893 0.110 0.00 68.35 c ATOM 754 C4' ADE 276 13 .964 -9 .087 -1.415 0.00 69.57 c ATOM 755 04' ADE 276 12 .697 -8, .626 -1.991 0.00 69.86 0 ATOM , . 756 Cl' ADE 276 12 .956 -7 .921 -3.216 0.00 70.40 c ATOM 757 C5 ADE 276 12 .348 -4 .304 -3.534 0.00 0.00 c ATOM 758 N7 ADE 276 12 .161 -4 .442 -2.189 0.00 0.00 N ATOM 759 C8 ADE 276 12 .359 -5 .715 -1.963 0.00 0.00 C ATOM 760 N9 ADE 276 12 .653 -6 .461 -3.074 0.00 0.00 N ATOM 761 Nl ADE 276 12 .512 -3 .357 -5.671 0.00 0.00 N ATOM 762 C2 ADE 276 12 .790 -4 .586 -6.118 0.00 0.00 C ATOM 763 N3 ADE 276 12 .882 -5 .735 -5.442 0.00 0.00 N ATOM 764 C4 ADE 276 12 .648 -5 .525 -4.125 0.00 0.00 C ATOM 765 C6 ADE 276 12 .270 -3 .151 -4.337 0.00 0.00 C ATOM 766 N6 ADE 276 11 .964 -1 .949 -3.763 0.00 0.00 N ATOM 767 C2' ADE 276 14 .429 -8 .212 -3.550 0.00 70.33 C ATOM 768 02' ADE 276 14 .557 -9 .452 -4.242 0.00 70.22 O ATOM 769 C3' ADE 276 15 .016 -8 .270 -2.146 0.00 70.19 C ATOM 770 03' ADE 276 16 .305 -8 .883 -2.131 0.00 71.00 O ATOM 771 1H5' ADE 276 13 .269 -9 .616 0.558 0.00 0.00 H ATOM 772 2H5' ADE 276 15 .006 -9 .145 0.485 0.00 0.00 H ATOM 773 H4' ADE 276 14 .062 -10 .166 -1.665 0.00 0.00 H ATOM 774 HI' ADE 276 12 .291 -8 .358 -3.992 0.00 0.00 H ATOM 775 H8 ADE 276 12 .313 -6 .193 -0.991 0.00 0.00 H ϊ ϊ s u ft O o o u u o ϋ z ϋ z υ z z u o ϋ z ϋ u o ϋ o a w K K ϊ s i K K ϊ K f c O o o u u o u z υ z u z z ϋ O ϋ z ϋ 90 © ϋ O O O O O O l-O CO CM CO LO ∞ CO cn o O O O O O O O O O O O rH rH cn O O O OO O O O O O i O O O O O O CO -n LO LD LO CM rH CO O O O O O O O O O O O Cn cn CO i-H O O O O O O O O O O U O O O O O O rH rH rH CM CO ^ t n in O O O O CD O O σ CD O ^-^ ^^ ^ CO O O CD O O O O σ O O CD CM CM CM CM rH O O Cn CD O O CD CD O CD Cn O CD Cn c a. r- r- r- r- r- r- r- r-- r-- r-- r-- r-- r^ r^ r^ Lo r- r^ r-~ r-~ r-~ 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CD Cn r^ O O O O C O O O C-5 θ r- r^ r^ LD '^ rO CM rH rH O rH CM rH O Cn CD rH rH CM CM O CD O CD O O O O O O O CD O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O CD O O O O CD O oc D oooσ o o ooooooooσoooooooo σooooooooooooooooooo O O O O O O O O O O O rH O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O rH O O O LD -n co o m m ro cn cM co rH rH LO CM ^ U-) CM in CO rH O LD rO CM rH rO Cn iH CM CM r-- CO CM O rH in CM r-- LD Cn in rO CM -n O CM rH r- CM Cn Cn LD O CO CM rH H o ^ r- pi ω io ^. o^ H σi tD i-' ^ H co o ^. iη -^ ω c- i ^ 'V o σi r' Ln in ri ^ N σi -- co r- ro ro r~- r— o co LD O ri ^ o - ^ -j iβ -q' ffi ω i o i co σi ^ CM σi H i io i ^ ω rj tη c co ω in i ^ -' cM csi m -^ m LD m LD ro LD rO 'T -o co ro ro cM CM o o o o o o O O rH rH I I I I I I I I I I I I I I I I I I I I I CO ^f rH CO CM r- H σl '^ ^D f LO ffl C , ^ σι co ^ , o lD ■ ω m c lΛ α) '. ^ f l O σl σι c] co σl ^ ω ω ι ( ro ι ( γ ^ G) co m m co ro 'ϊ 7 0 '» ^ <^' ι c^ι ι») n t^l -> ω ιη ιO ', •!f ', (Il n ^ H r- ', -l n c- ^ ln H ω n H ( , l r) Λ ^ ^£l M ■ 5T co m en rH H fO H ^B N ιn o -) ri ^ o o n ^ι •. I - ^ ι ι , l O O -) Ol p^ r ', m 1' t^ι co ri -l H -ι m ri tM rH O m m rH O σ cM c "=r , g , '=r θ rH rθ 'r' C rH o o -^ LD ^r t ^ co ro -π -O rH o o o -^ ro 1 1 1 1 1 I l l en LO CM r~ O ^ CD LD O -π θ3 CO O CM rH rH O rH rH LD O .^ CM ι→ O O LO CD rH LD rH LO Cn θ l^ ι '^ ^ oD a ) a ) O ^ ^ H H H oo ^ o ^ 'τ t ^ fO ι co ^D (Λ '^^ ω o ^ ol ιn to ιn ω σl σl σl ιη f ι ^^ r • ι τ ) H c! ιn ^ M ^ ^ o in H H O in iO T ri r t- σi ω -i iD csi co H N ω 'Φ to ^ o σi O H m rj tΛ - i tη tΩ -' H o csi H o r- O H CM O CM O CO I— CO f— CO O rH rH rO 'in CO rO CO rO rH rH rH rH CD O σ O σ O CO CO CO m cM 'ϋ' CO CD rH o rH co ro ^q 1 in CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM Cxl CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM co oo co co co co co oo- co co co co co cD cn cn cTϊ σ^ cn cn cn cn cn cn cn cn cn cn cn cn cn cn cn σ^ cn cn cn cn cn c- cn cn cn cn cn cn t^ r-- r~ r-- r^ r-- r-- r^ r^ r-- [^ r^ r^ r^ r^ r-- t^ r^ r~ r^ r^ r^ r^ [^ r-- r^ CM CM CM CN CM CN CM CM CM CM CM CM CM CN CM CN CM CN CM CN CM CM CM C CM CM CM CM CM CM CM CM CM CM CM C\| CM CM CM C^ C P C PC PC C PC P P C E H - H H E H H E H - H E H H E H E H EH EH E H - H - H - H - H H EH E H EH EH EH EH -H -H EH H EH H EH CM ro ro -o m ^r rH EC EC EC EC CM CM ro H CM t m '^r ^r H S O O O Z O 25 CM CM ro ro m m ^r- rH EC EC EC EC CM CM CO CO O O EC EC EC EC rH CM EC O EC O O O O O O O O O EC EC EC EC rH CM EC O EC O EC rH CM EC EC i fl r- o oι θ H o H fO [ ιη n '7 '. ω co LO ω ω o j m oD ω ω © o 222222222222222222222222222222222 S 2222222 S 2222 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O OO O O O O O Q cM -o -n co CO rO rH Cn LO Cn rH rH -n '^' rH CM r-- LO CM Lo rn m ^ ■ ^ ^r O O O O O O O -O CO O rH Cn O '3' 0 0 -O rH CO rH rH LO r-~ cn c c 'τ r--- r-- D ro -n -o cM Lθ ro o co cn r^ oo co co cn cn -n rH cn oι ιn - l iD ^ m o -ι t. r-- o cM co o cM "=r -n LD o r-- o -n -n r- CM ro r--- ^j' -n co Lθ r-~ co co r- r-- -o ^< *q ι -n ro cM rH rθ CM ^ OO Cn -O O rH O Cn LD LO L r-'- o LD ro cn LD cM -o o ro co Lo Lθ - Lθ cn r-- o ^r o c LD - -n ^r l -0 -0 -0 - LO .-- LD -0 -0 ^r' rH rH rH rH rH rH '^ 'ϊr 1 . '^ -o -o -n -o -n -n CM CM CM CM CM C CM CM CM CM CM CM CM CM CM CM CM CM CM RM CM CM CM CM PC PC PC PC PC H EH EH E H EH EH EH EH EH EH EH EH EH EH EH EH H >H >H >H H H H >H >H O CD CD O O O O O O O O O O O O O O O O O M si n ^r ^ i '^ 'α' rH Z O O O Z O S-i O rH CM rθ '5τ , -θ Lθ r-- CD c θ rH CM '^ t =r ^r ^j , ^r 'r ^r ϊ =τ , ^ι , -n -o -o M AT O C C ATOM 56 03' CYT 254 12.919 8.982 3.021 0.00 58.24 0 ATOM 57 1H5' CYT 254 14.250 8.970 6.940 0.00 0.00 H ATOM 58 2H5' CYT 254 12.793 9.303 5.930 0.00 0.00 H ATOM 59 H4' CYT 254 14.903 9.597 4.627 0.00 0.00 H ATOM 60 HI' CYT 254 16.987 7.275 3.483 0.00 0.00 H ATOM 61 H6 CYT 254 14.576 5.555 5.586 0.00 0.00 H ATOM 62 1H4 CYT 254 15.115 1.003 4.908 0.00 0.00 H ATOM 63 2H4 CYT _ 254 16.056 0.819- 3.460 0.00 0.00 H ATOM 64 H5 CYT " 254 14.409 3.103 5.774 0.00 0.00 H ATOM 65 H2' CYT 254 14.733 6.954 1.926 1.00 0.00 H ATOM 66 H02' CYT 254 14.837 9.293 1.721 0.00 0.00 H ATOM 67 H3' CYT 254 13.271 7.074 3.885 0.00 0.00 H ATOM 68 P CYT 255 11.514 8.530 2.443 0.00 58.36 P ATOM 69 OIP CYT 255 10.721 9.742 2.135 0.00 58.73 O ATOM 70 02P CYT 255 10.904 7.533 3.351 0.00 57.89 O ATOM 71 05' CYT 255 11.907 7.811 1.086 0.00 58.47 O ATOM 72 C5' CYT 255 12.346 8.631 0.005 0.00 59.01 C ATOM 73 C4' CYT 255 13.066 7.819 -1.082 0.00 59.66 C ATOM 74 04' CYT 255 14.173 7.038 -0.524 0.00 59.98 O ATOM 75 Cl' CYT 255 14.257 5.775 -1.208 0.00 60.44 C ATOM 76 Nl CYT 255 14.014 4.598 -0.300 0.00 0.00 N ATOM 77 C6 CYT 255 13.387 4.667 0.941 0.00 0.00 C ATOM 78 C2 CYT 255 14.334 3.307 -0.839 0.00 0.00 C ATOM 79 02 CYT 255 14.845 3.184 -1.967 0.00 0.00 O ATOM 80 N3 CYT 255 14.054 2.191 -0.081 0.00 0.00 N ATOM 81 C4 CYT 255 13.479 2.281 1.143 0.00 0.00 C ATOM 82 N4 CYT 255 13.240 1.169 1.894 0.00 0.00 N ATOM 83 C5 CYT 255 13.116 3.574 1.673 0.00 0.00 C ATOM 84 C2' CYT 255 13.246 5.868 -2.363 0.00 60.12 C ATOM 85 02' CYT 255 13.854 6.446 -3.518 0.00 59.65 O ATOM 86 C3' CYT 255 12.191 6.773 -1.748 0.00 60.02 C ATOM 87 03' CYT 255 11.326 7.329 -2.739 0.00 59.53 O ATOM 88 1H5* CYT 255 13.048 9.422 0.359 0.00 0.00 H ATOM 89 2H5' CYT 255 11.466 9.135 -0.455 0.00 0.00 H ATOM 90 H4' CYT 255 13.504 8.505 -1.839 0.00 0.00 H ATOM 91 HI' CYT 255 15.290 5.714 -1.614 0.00 0.00 H ATOM 92 H6 CYT 255 13.118 5.658 1.294 0.00 0.00 H ATOM 93 1H4 CYT 255 13.501 0.271 1.536 0.00 0.00 H ATOM 94 2H4 CYT 255 12.811 1.250 2.793 0.00 0.00 H ATOM 95 H5 CYT 255 12.634 3.646 2.649 0.00 0.00 H ATOM 96 H2' CYT 255 12.876 4.878 -2.630 1.00 0.00 H ATOM 97 H02' CYT 255 13.126 6.823 -4.019 0.00 0.00 H ATOM 98 H3' CYT 255 11.640 6.204 -0.960 0.00 0.00 H ATOM 99 P GUA 256 9.835 6.802 -2.848 0.00 59.25 P ATOM 100 OIP GUA 256 9.181 7.458 -4.001 0.00 59.56 O ATOM 101 02P GUA 256 9.183 6.936 -1.526 0.00 59.17 O ATOM 102 05' GUA 256 10.014 5.259 -3.163 0.00 59.81 O ATOM 103 C5' GUA 256 10.503 4.868 -4.441 0.00 60.87 C ATOM 104 C4' GUA 256 10.741 3.349 -4.526 0.00 61.59 C ATOM 105 04' GUA 256 11.604 2.863 -3.450 0.00 61.62 O ATOM 106 Cl' GUA 256 11.138 1.579 -3.005 0.00 62.16 C ATOM 107 N9 GUA 256 10.740 1.655 -1.566 0.00 0.00 N ATOM 108 C4 GUA 256 10.729 0.581 -0.653 0.00 0.00 C ATOM 109 N3 GUA 256 11.115 -0.706 -0.869 0.00 0.00 N ATOM 110 C2 GUA 256 11.038 -1.506 0.236 0.00 0.00 C ATOM 111 Nl GUA 256 10.552 -0.997 1.455 0.00 0.00 N ATOM 112 N2 GUA 256 11.412 -2.813 0.321 0.00 0.00 N ATOM 113 C6 GUA 256 10.126 0.338 1.694 0.00 0.00 C ATOM 114 06 GUA 256 9.719 0.737 2.791 0.00 0.00 O ATOM 115 C5 GUA 256 10.254 1.127 0.544 0.00 0.00 C z u υ o o o κ ϊ ; i ! 3! 3! K 3 ; 5 ; ϊ 3 ; κ n o o o u ϋ θ ϋ u z u z z ϋ z o u z o θ ϋ θ a! 3i j; a; s κ ϊ « ϊ; κ s ». o o o u ϋ θ u z u 90 © ca O o o CM ro m r— CD O CD O CD O CD O O O O CO CO LD CD CO LO rH r— O LO LO LD rH CM -0 «=T L0 LD LD CM CD O O O CD O O O O O L0 r0 CM LD r— LD Cn rO CD H CD H in n ^ O O O O O O O CD O CD CD CO LD ^r' CM O rH CD rH LD CM LD r H CO -5T -=I , rH rH '=r rH CD O O O O O O O O O O O CM eM Cn ^r r- LD r- CO -vI' U α. o o o o o o o o o cM ro cM ro co co r r LD LO -5i' 'vr LO LO -o -O LD r--- ro cM co ro o o o o o ' 0 o o ro ^o ro ro ro * ; ^ '=r ^r ^r ^τ , LO LO LD LD LD LD LD LO LO LD LD LD LD -O LO LO LD LO LD LD LD LD LD LQ LO LD LD LD LO LD LO LO LD LO LD LD o o cp o o o o o o o cD o o o o o o o o o o o o o o o o o o o cD O O O o cD O O o o o o o o o o o o o o o σ σ o o σ o σ o o O O c O O O Q O O CD O CD O CD O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O rH O O O O O O O O O O O O O O O O O O O O O O O O CD O O O O CD O O rH O O O O O O O O O O O O rH ro co rH LD "a i in co ^-' cn o LD in o cM r-- co LD co LO LD ^ co -n r-~ rH in o cn cM ro LD CD in in O ^ LO er> ιn LD LO CM CD O - CD OO CM LO OO CO CO CΛ in r-~ CM -^ CO ^ Cn LD [^ r- CO CO rH CM r~ -^ •^ co e o m -O LO C , ^ H CM H ^ rO ' ^ r-- ^ '^ D co o - o rO rH i LO r LD co r-- r- D r-~ 0 0 -0 -O ^ ιn ^ in -O rO CM rH O rH CO -O Cθ Lθ ^ LO .^ ^ rO CM .H O O rH O CM CM rH O .H rH rH O I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I ' I I I I I J I I I I I I I i eM co LD rH c -^ ro -^ r^ LD o -n tn c in rH c e CD c rH ^ cn rH O O cn cM rH D co i ro rH cM cn -o c t-^ LO in LD co i cn r^ rH rH r^ cn ro cn LO O 'Hi Ln co cM ' ^ co co cn H in in ^^ LD i in t^ « ^ ri ^ ln l r^ H O ω ιo ^n ^l ιs ln ιn Il ^ ^ m '* ιn cN n cM O O O H ^^ H ln '. ^ ^ m ' n ^ m ω c ^ N O o ^ O ln ω H ^ , l ^ ιn ιη ^ , l CM CM rH O CM CM in -n rO O rH rO CO CO O O CM CM rH CM rO -^ ^ CO rO O O rH CM O rH CM rH O I I I I I I I I en r- CO LO rH LO LD r CO ^r CM OO CO rH CO cM f-- r--- en o cn r-- -n -o co -o LD -n cM r-- Lo -o co cM r- o -n O m LD r~- LD CO CM CM r rH CO O LO CO rH O CD Cn oO LD CM i— r- en rH Lo o LD LO ' cn oo ro cn cn r-- LO c cM in - Lo ro rH ^n c r-- co ^r H CD r- D O C Co cD ^r - r^ oo co LD co r-- co rH cM ^r ^r rH ^r ^r , σ c c cD rH c cn cM cn - ' =3 ι r— 'a r~- C cn -!-' ro r- rH <^ co co rH LD ιn co ιn rH rH co r-- cM cn co ro t--- Lo cM co ro cn -o o ro r- "=r o θ rH co m t-- r- o r-- LD cn eo rH -n -o r— ^f rH Cn θ -n σ -n -O rH Cn rH rH O rH rH O O -n Cθ r-- LD LD LD in ιn tn -O LD l^ LD LD LO -0 -O LD LO r- LO LO LO LO LD LD LD LO LD LO LD LΩ LO LO LD LD LD LD r-- t''-- .''-- r'- r'- .-~ r ιn ιn ιn ιn -o ιn ιn ιn -θ Lθ in ιn ιn ιn ιn ιn ιn ιn -o -o ιn ιn ιn ιn -o ιn ιn ιn ιn ιn ιn ιn ιn ιn -^ pC r^ ^ pC p pC p PC pC p C pC PC pC w w w w w w w w w ω ω w ω CD CD CD CD CD CD CD. O O O U U O O O PC PC F^ PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC P^ t— CO - - - - - - ' - - rH CM CM CO - - - - - - - LO r- CO Cn rH CM CO '^ LO LD - - - - - - - - CO CM LO LD - - - CM CM CM - - - - - CT> * 3 " Z U N N n m i fl in ^ H E M B K N fn rH CM -O -O ^ ^ rH S S S O S Z C C rO in in ^ iH EC EC EC E C CM C rH CM -O -O '^ 'α' rH lS O O O O O EC EC EC EC rH CM EC O EC O O O O O O O O O O O EC EC CC EC rH CM EC O EC O O O O O O O rH CM EC rH CM EC -^ ^ ∞ m o ri N ci f in c-' ω m o ri N ro ^ in ^ ∞ m o H N c 'ϊ in iO ω m o H N ^ in -i ω cri o H iN c ^ in -i h ω m o H .i n ' , ^ rH rH rH c C C C CM CM C C CM CM c o ro r o cθ c o ro r '^ '^ ^r , *^ *^ ^ ^ ^r '^ ^ , -θ ιn -θ ι ι^ © o 222222222222222222222222222222222222222222222222222222222222 OOtiOOlHOOOtHOOrlO EOHOHOtlOhOhO tOHOEHOEHOhOfHOriOhOhOhOEH rOlOlHOrlOh rOlO HOOlHOrl EOHOhOOOOOOOOOOOOOOOOOOOOOOO PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC PC P^ ATOM 176 N3 GUA 258 1.,542 2.357 2.816 0.00 63.91 N ATOM 177 C2 GUA 258 1, .917 1.521 3.814 0.00 63.72 C ATOM 178 Nl GUA 258 1. .421 1.691 5.121 0.00 64.00 N ATOM 179 N2 GUA 258 2. .786 0.487 3.688 0.00 63.25 N ATOM 180 C6 GUA 258 0, .531 2.718 5.548 0.00 64.06 C ATOM 181 06 GUA 258 0, .132 2.832 6.712 0.00 63.17 O ATOM 182 C5 GUA 258 0. ,199 3.575 4.488 0.00 64.23 c ATOM 183 N7 .GUA 258 -0. .608 4.680 4.502 0.00 64.22 N ATOM 184 C8 GUA 258 -0. .592 5.116 3.265 0.00 64.55 C ATOM 185 C2* GUA 258 -0. .298 5.648 0.210 0.00 64.98 C ATOM 186 02' GUA 258 -1. .712 5.498 0.149 0.00 65.30 O ATOM 187 C3' GUA 258 0. .453 5.530 -1.124 0.00 65.31 C ATOM 188 03' GUA 258 0. .161 4.345 -1.854 0.00 66.59 O ATOM 189 1H5' GUA 258 1. .869 7.530 -0.171 0.00 0.00 H ATOM 190 2H5' GUA 258 3. .388 6.687 0.262 0.00 0.00 H ATOM 191 ' H4' GUA 258 2. ,505 4.706 -1.250 0.00 0.00 H ATOM 192 HI' GUA 258 0. .200 3.543 0.476 0.00 0.00 H ATOM 193 HI GUA 258 1. .736 1.057 5.844 0.00 0.00 H ATOM 194 1H2 GUA 258 3. .175 0.274 2.790 0.00 0.00 H ATOM 195 2H2 GUA 258 3. .025 -0.077 4.481 0.00 0.00 H ATOM 196 H8 GUA 258 -1, .157 5.962 2.874 0.00 0.00 H ATOM 197 H2' GUA 258 -0. .085 6.587 0.720 1.00 0.00 H ATOM 198 H02' GUA 258 -1. .877 4.712 -0.384 0.00 0.00 H ATOM 199 H3' GUA 258 0. .322 6.431 -1.760 0.00 0.00 H ATOM 200 P URA 259 -1. .132 4.112 -2.710 0.00 67.33 P ATOM 201 OIP URA 259 -1. .522 5.370 -3.385 0.00 67.46 O ATOM 202 02P URA 259 -2, .136 3.451 -1.846 0.00 6.7.83 O ATOM 203 05' URA 259 -0. .606 3.067 -3.771 0.00 67.75 O ATOM 204 C5' URA 259 0, .003 3.536 -4.970 0.00 68.49 c ATOM 205 C4' URA 259 1, .162 2.637 -5.420 0.00 69.20 c ATOM 206 04' URA 259 2. .318 2.773 -4.540 0.00 69.18 0 ATOM 207 Cl' URA 259 2. .975 1.495 -4.423 0.00 69.15 c ATOM 208 Nl URA 259 2, .968 0.994 -3.001 0.00 68.67 N ATOM 209 C6 URA 259 2. .200 1.564 -1.978 0.00 68.48 c ATOM 210 C2 URA 259 3. .862 -0.081 -2.699 0.00 68.09 c ATOM 211 ■ 02 URA 259 4, .560 -0.665 -3.533 0.00 67.78 0 ATOM 212 N3 URA 259 3. .884 -0.461 -1.336 0.00 67.84 N ATOM 213 C4 URA 259 3. .125 0.101 -0.280 0.00 68.39 C ATOM 214 04 URA 259 3, .220 -0.328 0.873 0.00 68.79 O ATOM 215 C5 URA 259 2. .251 1.186 -0.685 0.00 68.73 C ATOM 216 C2' URA 259 2, .257 0.570 -5.430 0.00 69.56 C ATOM 217 02' URA 259 2, .834 0.684 -6.729 0.00 69.66 O ATOM 218 C3' URA 259 0, .854 1.152 -5.371 0.00 69.75 C ATOM 219 03' URA 259 0 .024 0.743 -6.457 0.00 71.19 O ATOM 220 1H5' URA 259 0, .387 4.580 -4.880 0.00 0.00 H ATOM 221 2H5' URA 259 -0 .770 3.531 -5.770 0.00 0.00 H ATOM 222 H4' URA 259 1, .502 2.943 -6.433 0.00 0.00 H ATOM 223 HI' URA 259 4 .027 1.652 -4.746 0.00 0.00 H ATOM 224 H6 URA 259 1, .535 2.360 -2.291 0.00 0.00 H ATOM 225 H3 URA 259 4 .488 -1.234 -1.087 0.00 0.00 H ATOM 226 H5 URA 259 1 .631 1.677 0.066 0.00 0.00 H ATOM 227 H2' URA 259 2 .329 -0.473 -5.121 1.00 0.00 H ATOM 228 H02' URA 259 2 .165 0.348 -7.330 0.00 0.00 H ATOM 229 H3' URA 259 0 .418 0.897 -4.374 0.00 0.00 H ATOM 230 P ADE 260 -1 .119 -0.326 -6.198 0.00 72.35 P ATOM 231 OIP ADE 260 -1 .958 -0.423 -7.414 0.00 72.16 O ATOM 232 02P ADE 260 -1 .802 -0.017 -4.922 0.00 71.24 O ATOM 233 05' ADE 260 -0 .294 -1.667 -6.021 0.00 72.02 O ATOM 234 C5' ADE 260 0 .334 -2.206 -7.183 0.00 72.26 C ATOM 235 C4' ADE 260 1 .244 -3.391 -6.837 0.00 72.45 C ATOM 236 04' ADE 260 2.253 -3.015 -5.842 0.00 72.73 0 ATOM 237 Cl' ADE 260 2. ,381 -4.066 -4.871 0.00 72.84 c ATOM 238 C5 ADE 260 1. 322 -3.560 -1.378 0.00 73.64 c ATOM 239 N7 ADE 260 0. ,980 -2.342 -1.894 0.00 73.11 N ATOM 240 C8 ADE 260 1. 302 -2.426 -3.160 0.00 72.80 c ATOM 241 N9 ADE 260 1. 865 -3.617 -3.537 0.00 73.10 N ATOM 242 Nl ADE 260 1. ,609 -5.338 0.119 0.00 74.80 N ATOM .243 C2 ADE 260 2. ,125 -6.026 -0.904 0.00 74.11 c ATOM 244 N3 ADE 260 2. ,312 -5.648 -2.170 0.00 73.90 N ATOM 245 C4 ADE 260 1. 875 -4.380 -2.354 0.00 73.44 c ATOM 246 C6 ADE 260 1. ,184 -4.049 -0.066 0.00 74.18 c ATOM 247 N6 ADE 260 0. ,661 -3.243 0.906 0.00 74.42 N ATOM 248 C2' ADE 260 1. 627 -5.267 -5.469 0.00 72.52 c ATOM 249 02' ADE 260 2. 463 -5.994 -6.368 0.00 72.26 0 ATOM 250 C3' ADE 260 0. ,498 -4.544 -6.187 0.00 72.34 c ATOM 251 03' ADE 260 -0, ,160 -5.380 -7.138 0.00 72.21 0 ATOM 252 1H5' ADE 260 0. .952 -1.432 -7.694 0.00 0.00 H ATOM 253 2H5' ADE 260 -0. ,443 -2.558 -7.901 0.00 0.00 H ATOM 254 H4' ADE 260 1. .793 -3.733 -7.741 0.00 0.00 H ATOM 255 HI' ADE 260 3. .463 -4.302 -4.783 0.00 0.00 H ATOM 256 H8 ADE 260 1, .135 -1.655 -3.907 0.00 0.00 H ATOM 257 H2 ADE 260 2. .440 -7.043 -0.670 0.00 0.00 H ATOM 258 1H6 ADE 260 0. .366 -2.313 0.683 0.00 0.00 H ATOM 259 2H6 ADE 260 0. .581 -3.580 1.847 0.00 0.00 H ATOM 260 H2' ADE 260 1, .300 -5.949 -4.684 1.00 0.00 H ATOM 261 H02' ADE 260 1, .857 -6.467 -6.944 0.00 0.00 H ATOM 262 H3' ADE 260 -0. ,201 -4.133 -5.420 0.00 0.00 H ATOM 263 P GUA 261 -1, .720 -5.641 -7.030 0.00 1.00 P ATOM 264 OIP GUA 261 -2, .117 -6.583 -8.099 0.00 1.00 O ATOM 265 02P GUA 261 -2, .424 -4.342 -6.968 0.00 1.00 O ATOM 266 05' GUA 261 -1, .868 -6.360 -5.626 0.00 1.00 O ATOM 267 C5' GUA 261 -1, .328 -7.667 -5.469 0.00 1.00 C ATOM 268 C4' GUA 261 -1, .197 -8.050 -3.987 0.00 1.00 C ATOM 269 04 ' GUA 261 -0. .450 -7.040 -3.235 0.00 1.00 O ATOM 270 Cl' GUA 261 -1. .072 -6.831 -1.959 0.00 1.00 C ATOM 271 N9 GUA 261 -1. .638 -5.448 -1.872 0.00 1.00 N ATOM 272 C4 GUA 261 -2, .178 -4.853 -0.715 0.00 1.00 C ATOM 273 N3 GUA 261 -2, .283 -5.390 0.529 0.00 1.00 N ATOM 274 C2 GUA 261 -2. .869 -4.570 1.446 0.00 1.00 C ATOM 275 Nl GUA 261 -3, .297 -3.280 1.081 0.00 1.00 N ATOM 276 N2 GUA 261 -3, .115 -4.866 2.753 0.00 1.00 N ATOM 277 C6 GUA 261 -3, .195 -2.699 -0.211 0.00 1.00 C ATOM 278 06 GUA 261 -3, .609 -1.566 -0.484 0.00 1.00 O ATOM 279 C5 GUA 261 -2, .592 -3.579 -1.119 0.00 1.00 C ATOM 280 N7 GUA 261 -2, .331 -3.378 -2.442 0.00 1.00 N ATOM 281 C8 GUA 261 -1 .776 -4.493 -2.841 0.00 1.00 C ATOM 282 C2' GUA 261 -2 .108 -7.957 -1.819 0.00 1.00 C ATOM 283 02' GUA 261 -1. .501 -9.131 -1.282 0.00 1.00 O ATOM 284 C3' GUA 261 -2 .532 -8.135 -3.270 0.00 1.00 C ATOM 285 03' GUA 261 -3 .168 -9.389 -3.513 0.00 1.00 O ATOM 286 1H5' GUA 261 -0 .316 -7.742 -5.932 0.00 0.00 H ATOM 287 2H5' GUA 261 -1 .992 -8.406 -5.972 0.00 0.00 H ATOM 288 H4' GUA 261 -0 .636 -9.004 -3.886 0.00 0.00 H ATOM 289 HI' GUA 261 -0 .286 -6.948 -1.185 0.00 0.00 H ATOM 290 HI GUA 261 -3 .739 -2.697 1.779 0.00 0.00 H ATOM 291 1H2 GUA 261 -2 .849 -5.759 3.117 0.00 0.00 H ATOM 292 2H2 GUA 261 -3 .570 -4.200 3.347 0.00 0.00 H ATOM 293 H8 GUA 261 -1 .429 -4.707 -3.847 0.00 0.00 H ATOM 294 H2' GUA 261 -2 .916 -7.652 -1.154 1.00 0.00 H ATOM 295 H02' GUA 261 -2 .097 -9.847 -1.514 0.00 0.00 H ATOM 296 H3' GUA 261 -3.167 -7.265 -3.568 0.00 0.00 H ATOM 297 P CYT 262 -5.081 -9.540 -4.247 0.00 0.00 P ATOM 298 OIP CYT 262 -6.270 -10.336 -4.622 0.00 0.00 0 ATOM 299 02P CYT 262 -4.900 -8.232 -4.918 0.00 0.00 0 ATOM 300 05' CYT 262 -5.086 -9.303 -2.682 0.00 0.00 0 ATOM 301 C5' CYT 262 -5.252 -10.416 -1.809 0.00 0.00 c ATOM 302 C4' CYT 262 -5.647 -9.996 -0.382 0.00 0.00 • c ATOM 303 04' CYT 262 -.4.774 -8.941 0.148 o.σo 0.00 0 ATOM 304 Cl' CYT 262 -5.566 -8.005 0.909 0.00 0.00 c ATOM 305 Nl CYT 262 -5.626 -6.642 0.263 0.00 0.00 N ATOM 306 C6 CYT 262 -5.245 -6.389 -1.052 0.00 0.00 c ATOM 307 C2 CYT 262 -6.220 -5.575 1.026 0.00 0.00 c ATOM 308 02 CYT 262 -6.557 -5.733 2.215 0.00 0.00 0 ATOM 309 N3 CYT 262 -6.418 -4.355 0.407 0.00 0.00 N ATOM 310 C4 CYT 262 -6.079 -4.152 -0.892 0.00 0.00 c ATOM 311 N4 CYT 262 -6.311 -2.963 -1.519 0.00 0.00 N ATOM 312 C5 CYT 262 -5.453 -5.207 -1.648 0.00 0.00 c ATOM 313 C2' CYT 262 -6.947 -8.675 1.055 0.00 0.00 c ATOM 314 02' CYT 262 -6.960 -9.573 2.164 0.00 0.00 0 ATOM 315 C3' CYT 262 -7.046 -9.402 -0.278 0.00 0.00 c ATOM 316 03' CYT 262 -8.058 -10.409 -0.292 0.00 0.00 0 ATOM 317 1H5' CYT 262 -4.290 -10.971 -1.752 0.00 0.00 H ATOM 318 2H5' CYT 262 -6.031 -11.117 -2.189 0.00 0.00 H ATOM 319 H4' CYT 262 -5.549 -10.866 0.303 0.00 0.00 H ATOM 320 HI' CYT 262 -5.078 -7.914 1.904 0.00 0.00 H ATOM 321 H6 CYT 262 -4.709 -7.181 -1.565 0.00 0.00 H ATOM 322 1H4 CYT 262 -6.731 -2.205 -1.017 0.00 0.00 H ATOM 323 2H4 CYT 262 -6.047 -2.840 -2.475 0.00 0.00 H ATOM 324 H5 CYT 262 -5.129 -5.025 -2.674 0.00 0.00 H ATOM 325 H2' CYT 262 -7.725 -7.928 1.215 1.00 0.00 H ATOM 326 H02' CYT 262 -7.757 -10.098 2.052 0.00 0.00 H ATOM 327 H3' CYT 262 -7.178 -8.655 -1.098 0.00 0.00 H ATOM 328 P GUA 263 -9.489 -10.104 -0.906 0.00 1.00 P ATOM 329 OIP GUA 263 -10.190 -11.389 -1.125 0.00 1.00 0 ATOM 330 02P GUA - 263 -9.346 -9.202 -2.070 0.00 1.00 0 ATOM 331 05' GUA 263 -10.223 -9.308 0.253 0.00 1.00 0 ATOM 332 C5' GUA 263 -10.651 -10.034 1.402 0.00 1.00 c ATOM 333 C4' GUA 263 -11.054 -9.104 2.559 0.00 1.00 c ATOM 334 04' GUA 263 -10.004 -8.121 2.842 0.00 1.00 0 ATOM 335 Cl' GUA 263 -10.608 -6.850 3.134 0.00 1.00 c ATOM 336 N9 GUA 263 -10.302 -5.856 2.059 0.00 1.00 N ATOM 337 C4 GUA 263 -10.595 -4.478 2.108 0.00 1.00 c ATOM 338 N3 GUA 263 -11.204 -3.786 3.108 0.00 1.00 N ATOM 339 C2 GUA 263 -11.373 -2.458 2.849 0.00 1.00 c ATOM 340 Nl GUA 263 -10.909 -1.902 1.642 0.00 1.00 N ATOM 341 N2 GUA 263 -11.975 -1.545 3.662 0.00 1.00 N ATOM 342 C6 GUA 263 -10.246 -2.605 0.600 0.00 1.00 c ATOM 343 06 GUA 263 -9.821 -2.068 -0.428 0.00 1.00 0 ATOM 344 C5 GUA 263 -10.126 -3.965 0.896 0.00 1.00 c ATOM 345 N7 GUA 263 -9.595 -4.949 0.118 0.00 1.00 N ATOM 346 C8 GUA 263 -9.725 -6.036 0.831 0.00 1.00 c ATOM 347 C2' GUA 263 -12.110 -7.134 3.293 0.00 1.00 c ATOM 348 02' GUA 263 -12.408 -7.550 4.625 0.00 1.00 0 ATOM 349 C3' GUA 263 -12.289 -8.257 2.280 0.00 1.00 c ATOM 350 03' GUA 263 -13.504 -8.978 2.489 0.00 1.00 0 ATOM 351 1H5' GUA 263 -9.838 -10.702 1.770 0.00 0.00 H ATOM 352 2H5' GUA 263 -11.526 -10.670 1.138 0.00 0.00 H ATOM 353 H4' GUA 263 -11.196 -9.698 3.488 0.00 0.00 H ATOM 354 HI' GUA 263 -10.177 -6.494 4.095 0.00 0.00 H ATOM 355 HI GUA 263 -11.046 -0.913 1.485 0.00 0.00 H E α E C -C E C E C o- 1 o o o o o o o z o o o s o o o o θ o θ EC EC EC κ εc εc Eα εα Eπ :ι, θj θ θ θ o o o o s o o o :s o r- 90 © CO O O O O O O O O O O O O O O O O O O O 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H ]3 μ 3- 3a 3- ι-33 ι-33 ιι--33 μ 3_ ι-33 ι-33 μ3 43 3] *33 3 3 ^ 3 3 3 , 3 μ 33 HH μ 3 ι-33 ι.j3 f _3a | _ H μ 3 3 μ 3 μ _ 3 μ 3 H 3 3 3 3 H 3 3 3 ι-3 3 H 3 3 o o o o o o o o o o o O o o O O O O O O o o o o O O O O O O O 22222222222 2 S 22 2 2 2 2 2 2222 2222 o o o d d d d ό d d d d d d d d b d d d d d d d 2 2 2 2 2 2 22222222 S 222 S S 2 --; 2 S --: S S S 2 S S Uι -n W ( Jι -ι Ui ljπ - i ( ι Oι -ι -n ljι ϋι -π -ι -l Uι -ι -ι ϋπ -π -π W -l -l U-ιl U-nl U-πi WUl U Ul UHJl Ul Ul -. -i J- -> -% J- αJ--=. -- 1 - J--S. »J-- , -M- 1 . --- 1 . -_. M-. t--. --. --. -_. c-o C ) ω ω LΛ ) ω t 3 rθ [L o ro M to t t 3 -' j j μ j μ j μ j μ j μ J μ J θO OO OO oO oO θO OO OO OO OO LDD LLDD LLDD LLDD -DD LL^D LO LD LD LD CD OO co co m ro co co co v —iJ - -jJ ^ -Ji - -Jj -7i j-. ω t μ J CD LD -D -o c -n J^ --) ro μJ θ LD Co -J c <-π --. (jj to μ-" lD G ^l CMJl -> ω i- μ θ l CO ! Ul -ι LJ I. μ θ -ι ω cn t-π >ι=» ω .o .- » o _ c ' o ~ c-o- -j en tc to μ-> EC ro O O O O O O O EC O EC M μ EC EC EC EC O π o O — _ O O O O O O O EC O EC NJ μ Ed EC EC EC O O O 0 0 0 -2 μ-' J=> 'β» -π -n to μ-ι U M M E M a tπ μ fc ϋl -i U J M N f) 3 π θ O S I--1 0 -_; θ -3 μ J ιi^ Λ. αr -π r μ-' L. M M X a a X H J. ui ui L. i M ro ro en μ- 1 - - - - - rj -ι irJ - - - co t. t- μ co -J Ul Ol Ol M M I- lO b lD - - - - - l-rj rrj rj - _ . CO U M μ - - - - - - - G G G G G Ω Ώ ΏΏ Ώ Ω Ώ Ω Ώ Ώ Ω Ώ ΏΩ Ώ Ω Ω Ω Ω Ώ Ω Ώ Ώ Ώ Ω Ω Ώ Ω Ω Ώ Ω Ω Ω Ω ΩΏΩ Ω Ω Ώ Ώ Ω Ώ Ω Ω Ώ Ώ Ω SE- J F-?F? C?E : 9 999P9 G PP9 G G P9 G G G G G G G G GGGGGGGGGGGGGGGGGGGGGAG M to M M t to en cn cn cn cn cn LO L0 L0 LO L0 LD -J -J -J -J -J I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I μ-> μ j μ-> μ J j μ j μ j j μ J j μ j j μ j μ j μ-' μ j μ j μ j μ j μ j μ-' μ j μ-' μ-' μ j μ-' μ J μ-' j j j j μ j μ^ Cj --- _-. ( -o ro J r ι--. ro ω -jι i\-ι -ι (-π μ J Lθ M α-. -n crι i- J-. ω cn LJ (-ri t-ri ^ o -u --j (-n ro LO ^ O LD Ln ji e o c L7i 4-. -Aj -o j-> --> o »fc. c-π cσ -j -n ro - J — j o cn -i σi ^ i iD -i ω j i ∞ H j o o ui ω Nj w μ ϋi o ω M CD iD U Ln ra Nj ω ffi Λ μ o ^ u ω c i Nj t μ o ω i CD Cπ o — J o ω -jι e-π -j o --j -ϋ M -π cn - CD Co o o .-- -p ) M o ω ω σ -π o μ j --> oι r ^ μ- 1 μ-> μ- 1 μ-> μ-> I I I I I I I I M t ι o o o LD CD -- j -j e e cn J^ t M --» μ j L) c Ljι en π α-. M --) ω to μ J o o o o μ j ω UI O CJl LD -J ^ ^ ^ σi M LTl LD — I tO Cj rO CO LD CT l LD J^ O Cn C-o ω M M r --j o J^ »^ J^ J ιJ^ o^ LD θ LD CD c co μ j α-. o o LΛ) r co o cn co α-> L ι-^ Cjι cn r ) --. (-n co (^ α-> o to (^ π co π --. ro c r o μ j .r-. D LD r α-. o cn -J I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I Lo >ι^ c Ljι .J-> ji Lrι c-n -j -θ LD ∞ --J cn LJi W LΛj uι μ j >i^ uι cn J^ '-- cn c co cD -J Lri LD LD C-n -J -n μ-' μ-' LO LO — ι o ιjι θ -ι m cn H ^ -ι ιn c μ u ω iJ u μ ιc ^ -ι μ (j ijι M -> ι. ω μ -> Λ i. ω -ι μ ro *. o μ co ω co -i M U ω c^ ω ∞ u-» μ j co t M θ <-n ω uι o μ j Lji Lo o u μ j <-o -J -o -o co ω GJ C3 ^ CO ∞ μJ ι-^ π ω .-J CO LD .--. -π r μ J -O ~-- --J CO O l- C o o o o o o σ o o o o o o o μ j o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o μ j o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o σ o o o o o o o o o o o o o o o o o o o o o o cD O CD O O O CD O O O O O CD O O O O O O O O O O O O O O O O O CD O O O CD O CD O O O O O CD O O O O O O O O O O CD O CD O O O O CD O O to to ro O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O —J L LD O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O CD O O O O O O O O O CD O CD O O O O .-' .r-. CD 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 000 0 0000000000 000000000000000 0.0 --. --. O O O Z O O O O O O O ^ EC EC EC EC EC EC -C EC Eπ EC EC O O O O O Z O O O Z S O Z O SI O O O O O O O iT-' Eπ -C EC ffi ATOM 536 N3 URA 269 -15.314 12.658 -5.425 0.00 0.00 N ATOM 537 C4 URA 269 -16.001 12.231 -6.593 0.00 0.00 c ATOM 538 04 URA 269 -17.016 12.811 -6.988 0.00 0.00 0 ATOM 539 C5 URA 269 -15.408 11.078 -7.250 0.00 0.00 c ATOM 540 C2' URA 269 -13.042 8.836 -4.299 0.00 0.00 c ATOM 541 02' URA 269 -13.638 9.030 -3.020 0.00 0.00 0 ATOM 542 C3' URA , 269 -11.754 8.023 -4.264 0.00 0.00 c ATOM 543 03' URA 269 -10.935 8.419 -3.159 0.00 0.00 0 ATOM 544 1H5' URA 269 -10.724 7.693 -7.594 0.00 0.00 H ATOM 545 2H5' URA 269 -11.046 6.398 -6.383 0.00 0.00 H ATOM 546 H4' URA 269 -9.971 8.491 -5.452 0.00 0.00 H ATOM 547 HI' URA 269 -11.986 10.741 -4.194 0.00 0.00 H ATOM 548 H6 URA 269 -13.850 9.638 -7.217 0.00 0.00 H ATOM 549 H3 URA 269 -15.701 13.453 -4.938 0.00 0.00 H ATOM 550 H5 URA 269 -15.873 10.683 -8.154 0.00 0.00 H ATOM 551 H2' URA 269 -13.792 8.320 -4.898 1.00 0.00 H ATOM 552 H02' URA 269 -12.900 9.208 -2.431 0.00 0.00 H ATOM 553 H3' URA 269 -11.991 6.935 -4.239 0.00 0.00 H ATOM 554 P URA 270 -10.014 7.374 -2.745 0.00 1.00 P ATOM 555 OIP URA 270 -9.644 8.741 -2.315 0.00 1.00 0 ATOM 556 02P URA 270 -8.996 6.593 -3.482 0.00 1.00 0 ATOM 557 05' URA 270 -10.477 6.542 -1.482 0.00 1.00 0 ATOM 558 C5' URA 270 -11.403 7.137 -0.579 0.00 1.00 c ATOM 559 C4 ' URA 270 -11.967 6.110 0.414 0.00 1.00 c ATOM 560 04' URA 270 -12.617 4.987 -0.267 0.00 1.00 0 ATOM 561 Cl' URA 270 -12.280 3.757 0.398 0.00 1.00 c ATOM 562 Nl URA 270 -11.448 2.843 -0.472 0.00 1.00 N ATOM 563 C6 URA 270 -10.848 3.240 -1.673 0.00 1.00 c ATOM 564 C2 URA 270 -11.262 1.504 0.001 0.00 1.00 c ATOM 565 02 URA 270 -11.761 1.054 1.038 0.00 1.00 0 ATOM 566 N3 URA 270 -10.445 0.696 -0.827 0.00 1.00 N ATOM 567 04 URA 270 -9.819 1.077 -2.041 0.00 1.00 c ATOM 568 04 URA 270 -9.122 0.283 -2.680 0.00 1.00 0 ATOM 569 C5 URA 270 -10.079 2.445 -2.444 0.00 1.00 c ATOM 570 C2' URA 270 -11.592 4.186 1.711 0.00 1.00 c ATOM 571 02' URA 270 -12.563 4.426 2.729 0.00 1.00 0 ATOM 572 C3' URA 270 -10.891 5.460 1.264 0.00 1.00 c ATOM 573 03' URA 270 -10.519 6.317 2.340 0.00 1.00 0 ATOM 574 1H5' URA 270 -12.258 7.596 -1.126 0.00 0.00 H ATOM 575 2H5' URA 270 -10.893 7.942 -0.003 0.00 0.00 H ATOM 576 H4' URA 270 -12.742 6.585 1.054 0.00 0.00 H ATOM 577 HI' URA 270 -13.244 3.254 0.626 0.00 0.00 H ATOM 578 H6 URA 270 -11.049 4.255 -1.991 0.00 0.00 H ATOM 579 H3 URA 270 -10.286 -0.258 -0.533 0.00 0.00 H ATOM 580 H5 URA 270 -9.650 2.817 -3.374 0.00 0.Θ0 H ATOM 581 H2' URA 270 -10.914 3.407 2.059 1.00 0.00 H ATOM 582 H02' URA 270 . -12.070 4.812 3.459 0.00 0.00 H ATOM 583 H3' URA 270 -10.026 5.175 0.619 0.00 0.00 H ATOM 584 P GUA 271 -9.011 6.654 2.677 0.00 0.00 P ATOM 585 OIP GUA 271 -8.952 8.000 3.289 0.00 0.00 0 ATOM 586 02P GUA 271 -8.160 6.407 1.491 0.00 0.00 0 ATOM 587 05' GUA 271 -8.663 5.572 3.780 0.00 0.00 0 ATOM 588 C5' GUA 271 -9.357 5.629 5.026 0.00 0.00 c ATOM 589 C4' GUA 271 -9.639 4.229 5.590 0.00 0.00 c ATOM 590 04' GUA 271 -10.247 3.356 4.584 0.00 0.00 0 ATOM 591 Cl' GUA 271 -9.699 2.035 4.696 0.00 0.00 c ATOM 592 N9 GUA 271 -8.907 1.675 3.473 0.00 0.00 N ATOM 593 C4 GUA 271 -8.444 0.384 3.139 0.00 0.00 c ATOM 594 N3 GUA 271 -8.578 -0.767 3.853 0.00 0.00 N ATOM 595 C2 GUA 271 -8.019 -1.864 3.263 0.00 0.00 c ATOM 596 Nl GUA 271 -7.380 -1.755 2.015 0.00 0.00 N ATOM 597 N2 GUA 271 -7.997 -3.131 3.761 0.00 0.00 N ATOM 598 C6 GUA 271 -7.226 -0.565 1.254 0.00 0.00 c ATOM 599 06 GUA 271 -6.642 -0.522 0.165 0.00 0.00 0 ATOM 600 C5 GUA 271 ' -7.810 0.533 1.901 0.00 0.00 c ATOM 601 N7 GUA 271 -7.852 1.829 1.484 0.00 0.00 N ATOM . 602 C8 GUA 271 -8.492 2.462 2.433 0.00 0.00 c ATOM 603 C2' •GUA 271 -8.881 2.043 5.998 0.00 0.00 c ATOM 604 02 ' ' GUA 271 -9.711 1.731 7.116 ' 0.00 0.00 0 ATOM 605 C3' GUA 271 -8.389 3.486 6.026 0.00 0.00 c ATOM 606 03' GUA 271 -7.968 3.906 7.323 0.00 0.00 0 ATOM 607 1H5' GUA 271 -10.336 6.159 4.943 0.00 0.00 H ATOM 608 2H5' GUA 271 -8.737 6.194 5.757 0.00 0.00 H ATOM 609 H4' GUA 271 -10.361 4.300 6.433 0.00 0.00 H ATOM 610 HI' GUA 271 -10.559 1.336 4.787 0.00 0.00 H ATOM 611 HI GUA 271 -6.997 -2.591 1.593 0.00 0.00 H ATOM 612 1H2 GUA 271 -8.427 -3.325 4.643 0.00 0 . 00 H ATOM 613 2H2 GUA 271 -7.556 -3.872 3.250 0.00 0.00 H ATOM 614 H8 GUA 271 -8.706 3.527 2.449 0.00 0.00 H ATOM 615 H2' GUA 271 -8.078 1.307 5.953 1.00 0.00 H ATOM 616 H02' GUA 271 -9.199 1.991 7.886 0.00 0.00 H ATOM 617 H3' GUA 271 -7.593 3.607 5.252 0.00 0.00 H ATOM 618 ' P CYT 272 -6.201 3.803 7.461 0.00 1.00 P ATOM 619 OIP CYT 272 -5.796 4.449 8.729 0.00 1.00 O ATOM 620 02P CYT 272 -5.762 4.443 6.201 0.00 1.00 O ATOM 621 05' CYT 272 -5.701 2.298 7.467 0.00 1.00 O ATOM 622 C5' CYT 272 -5.871 1.513 8.644 0.00 1.00 C ATOM 623 C4' CYT 272 -5.693 0.008 8.369 0.00 1.00 C ATOM 624 04' CYT 272 -6.571 -0.445 7.285 0.00 1.00 O ATOM 625 Cl' CYT 272 -5.858 -1.343 6.417 0.00 1.00 C ATOM 626 Nl CYT 272 -5.638 -0.776 5.035 0.00 1.00 N ATOM 627 C6 CYT 272 -5.895 0.544 4.677 0.00 1.00 C ATOM 628 C2 CYT 272 -5.128 -1.673 4.033 0.00 1.00 C ATOM 629 02 CYT 272 -4.914 -2.875 4.283 0.00 1.00 O ATOM 630 N3 CYT 272 -4.901 -1.182 2.764 0.00 1.00 N ATOM 631 C4 CYT 272 -5.174 0.108 2.437 0.00 1.00 C ATOM 632 N4 CYT 272 -5.010 0.574 1.166 0.00 1.00 N ATOM 633 C5 CYT 272 -5.675 1.014 3.440 0.00 1.00 C ATOM 634 C2' CYT 272 -4.563 -1.682 7.172 0.00 1.00 C ATOM 635 02' CYT 272 -4.779 -2.771 8.068 0.00 1.00 O ATOM 636 C3' CYT 272 -4.296 -0.374 7.903 0.00 1.00 C ATOM 637 03' CYT 272 -3.389 -0.559 8.990 0.00 1.00 0 ATOM 638 1H5' CYT 272 -6.887 1.665 9.076 0.00 0.00 H ATOM 639 2H5' CYT 272 -5.122 1.825 9.406 0.00 0.00 H ATOM 640 H4 ' CYT 272 -5.974 -0.577 9.271 0.00 0.00 H ATOM 641 HI' CYT 272 -6.492 -2.253 6.330 0.00 0.00 H ATOM 642 H6 CYT 272 -6.341 1.175 5.435 0.00 0.00 H ATOM 643 1H4 CYT 272 -5.231 1.525 0.948 0.00 0.00 H ATOM 644 2H4 CYT 272 -4.673 -0.041 0.451 0.00 0.00 H ATOM 645 H5 CYT 272 -5.903 2.048 3.176 0.00 0.00 H ATOM 646 H2' CYT 272 -3.776 -1.962 6.472 1.00 0 . 00 H ATOM 647 H02' CYT 272 -4.108 -2.670 8.748 0.00 0.00 ' H ATOM 648 H3' CYT 272 -3.939 0.387 7.167 0.00 0.00 H ATOM 649 P GUA 273 -1.928 0.046 8.936 0.00 65.10 P ATOM 650 OIP GUA 273 -1.210 -0.342 10.170 0.00 64.77 O ATOM 651 02P GUA 273 -2.025 1.489 8.630 0.00 64.57 0 ATOM 652 05' GUA 273 -1.262 -0.692 7.701 0.00 64.14 0 ATOM 653 C5' GUA 273 -0.960 -2.080 7.786 0.00 62.38 c ATOM 654 C4 ' GUA 273 -0.565 -2.667 6.417 0.00 61.99 c ATOM 655 04 ' GUA 273 -1.601 -2.439 5.408 0.00 61.34 0 ATOM 656 Cl" GUA 273 1.003 -2.017 4.173 0.00 60.75 c ATOM 657 N9 GUA 273 1. 420 -0. 611 3. 858 0. 00 60. 16 N ATOM 658 C4 GUA 273 1. 406 0. 000 2. 584 0. 00 59. 63 C ATOM 659 ■ N3 GUA 273 0. 928 -0. 505 1. 413 0. 00 58. 77 N ATOM 660 C2 GUA 273 1. 126 0. 308 0. 331 o. 00 58. 33 C ATOM 661 Nl GUA 273 1. 742 1. 563 0. 483 0. 00 58. 87 N ATOM 662 N2 GUA 273 0. 800 0. 040 -0. 965 0. 00 57. 26 N ATOM . 663 C6 GUA 273 2. 236 2. 111 • 1. 696 0. 00 59 39 C ATOM 664 06 GUA 273 2. 813 3. 202 1. 768 0. 00 60. 03 O ATOM 665 C5 GUA 273 2. 033 1. 238 2. 770 0. 00 59. 49 C ATOM 666 N7 GUA 273 2. 403 1. 411 4. 068 0. 00 59. 69 N ATOM 667 C8 GUA 273 2. 038 0. 308 4. 663 0. 00 59. 91 C ATOM 668 C2' GUA 273 0 513 -2. 257 4. 340 0. 00 61. 01 c ATOM 669 02' GUA 273 0 845 -3. 592 3. 960 0. 00 60 10 0 ATOM 670 C3' GUA 273 0. 685 -2. 026 5. 839 0. 00 61. 69 c ATOM 671 03' GUA 273 1. 848 -2. 637 6. 399 0. 00 62. 51 0 ATOM 672 1H5' GUA 273 1 837 -2 650 8. 170 0. 00 0. 00 H ATOM 673 2H5' GUA 273 0. 114 -2. 232 8. 494 0. 00 0. 00 H ATOM 674 H4' GUA 273 0 440 -3 769 6. 496 0. 00 0. 00 H ATOM 675 HI' GUA 273 1 404 -2 686 3 382 0. 00 0 00 H ATOM 676 HI GUA 273 1. 894 2. 134 -0. 339 0. 00 0. 00 H ATOM 677 1H2 GUA 273 0 375 -0 836 -1. 204 0. 00 0. 00 H ATOM 678 2H2 GUA 273 1 024 0 694 -1. 689 0. 00 0. 00 H ATOM 679 H8 GUA 273 2 246 0 059 5 696 0 00 0 00 H ATOM 680 H2' GUA 273 1 075 -1 564 3 713 1 00 0 00 H ATOM 681 H02' GUA 273 1 751 -3 726 4 256 0 00 0 00 H ATOM 682 H3' GUA 273 0 652 -0 929 6 039 0 00 0 00 H ATOM 683 P ADE 274 3 219 -1 854 6 459 0. 00 63 35 P ATOM 684 OIP ADE 274 4 117 -2 542 7 413 0 00 62 97 O ATOM 685 02P ADE 274 2 961 -0 413 6 679 0 00 63 64 O ATOM 686 05' ADE 274 3 751 -2 043 4 986 0 00 64 75 O ATOM 687 C5' ADE 274 5 004 -2 654 4 715 0 00 66 11 c ATOM 688 C4' ADE 274 4 886 -4 169 4 519 0 00 67 14 c ATOM 689 04 ' ADE 274 3 850 -4 490 3 532 0 00 68 13 0 ATOM 690 Cl' ADE 274 4 373 -5 422 2 575 0 00 68 71 c ATOM 691 C5 ADE 274 5 104 -4 329 -0 862 0 00 68 97 c ATOM 692 N7 ADE 274 4 802 -3 122 -0 301 0 00 69 49 N ATOM 693 C8 ADE 274 4 518 -3 403 0 947 0 00 69 25 c ATOM 694 N9 ADE 274 4 624 -4 729 1 273 0 00 69 39 N ATOM 695 Nl ADE 274 5 706 -5 .967 -2 427 0 00 69 .25 N ATOM 696 C2 ADE 274 5 587 -6 .857 -1 438 0 00 69 .22 C ATOM 697 N3 ADE 274 5 .252 -6 .666 -0 .158 0 .00 68 .91 N ATOM 698 C4 ADE 274 5 018 -5 .351 0 .075 0 00 69 .25 C ATOM 699 C6 ADE 274 5 466 -4 .638 -2 .188 0 00 68 .74 c ATOM 700 N6 ADE 274 5 .549 -3 .640 -3 .120 0 .00 68 .24 N ATOM 701 C2' ADE 274 5 .643 -5 .994 3 .224 0 .00 68 .48 C ATOM 702 02' ADE 274 5 .329 -7 .028 4 .155 0 .00 69 .65 0 ATOM 703 C3' ADE 274 6 .159 -4 .738 3 .906 0 .00 67 .76 C ATOM 704 03' ADE 274 7 .173 -5 .009 4 .874 0 .00 67 .35 0 ATOM 705 1H5' ADE 274 5 .754 -2 .436 5 .510 0 .00 0 .00 H ATOM 706 2H5' ADE 274 5 .397 -2 .208 3 .778 0 .00 0 .00 H ATOM 707 H4' ADE 274 4 .616 -4 .684 5 .464 0 .00 0 .00 H ATOM 708 HI' ADE 274 3 .612 -6 .219 2 .434 0 .00 0 .00 H ATOM 709 H8 ADE 274 4 .209 -2 .689 1 .710 0 .00 0 .00 H ATOM 710 H2 ADE 274 5 .798 -7 .890 -1 .715 0 .00 0 .00 H ATOM 711 1H6 ADE 274 5 .350 -2 .694 -2 .862 0 .00 0 .00 H ATOM 712 2H6 ADE 274 5 .815 -3 .858 -4 .058 0 .00 0 .00 H ATOM 713 H2' ADE 274 6 .314 -6 .417 2 .476 1 .00 0 .00 H ATOM 714 H02' ADE 274 6 .083 -1 .066 4 .749 0 .00 0 .00 H ATOM 715 H3' ADE 274 6 .507 -4 .035 3 .109 0 .00 0 .00 H ATOM 716 P ADE 275 8.663 -4.528 4.605 0.00 67.69 P ATOM 717 OIP ADE 275 9.472 -4.777 5.818 0.00 67.60 O ATOM 718 02P ADE 275 8.637 -3.147 4.071 0.00 67.94 0 ATOM . 719 05' ADE 275 9.155 -5.495 3.449 0.00 67.85 0 ATOM 720 C5' ADE 275 9.357 -6.871 3.752 0.00 67.53 c ATOM 721 C4' ADE 275 9.470 -7.730 2.481 0.00 67.23 c ATOM 722 04' ADE 275 8.323 -7.528 1.592 0.00 67.09 0 ATOM 723 Cl' ADE 275 8.780 -7.452 0.234 0.00 66.99 c ATOM 724 C5 ADE 275 8.672 -4.281 -1.636 0.00 67.99 c ATOM 725 N7 ADE 275 8.327 -3.821 -0.397 0.00 67.87 N ATOM 726 C8 ADE 275 8.304 -4.895 0.352 0.00 67.37 C ATOM 727 N9 ADE 275 8.639 -6.057 -0.294 0.00 67.47 N ATOM 728 Nl ADE 275 9.128 -4.354 -3.934 0.00 67.93 N ATOM 729 C2 ADE 275 9.292 -5.673 -3.790 0.00 68.10 C ATOM 730 N3 ADE 275 9.199 -6.425 -2.690 0.00 67.88 N ATOM 731 C4 ADE 275 8.871 -5.657 -1.622 0.00 67.85 C ATOM 732 C6 ADE 275 8.819 -3.577 -2.846 0.00 67.86 C ATOM 733 N6 ADE 275 8.651 -2.218 -2.863 0:00 68.36 N ATOM 734 C2' ADE 275 10.233 -7.953 0.269 0.00 66.60 C ATOM 735 02' ADE 275 10.280 -9.378 0.228 0.00 66.18 O ATOM 736 C3' ADE 275 10.673 -7.392 1.615 0.00 66.74 c ATOM 737 03' ADE 275 11.864 -7.995 2.117 0.00 66.98 0 ATOM 738 1H5' ADE 275 8.514 -7.273 4.361 0.00 0.00 H ATOM 739 2H5' ADE 275 10.293 -6.987 4.343 0.00 0.00 H ATOM 740 H4' ADE 275 9.477 -8.808 2.754 0.00 0.00 H ATOM 741 HI' ADE 275 8.147 -8.139 -0.368 0.00 0.00 H ATOM 742 H8 ADE 275 8.001 -4.935 1.393 0.00 0.00 H ATOM 743 H2 ADE 275 9.549 -6.212 -4.702 0.00 0.00 H ATOM 744 1H6 ADE 275 8.421 -1.737 -2.016 0.00 0.00 H ATOM 745 2H6 ADE 275 8.759 -1.713 -3.718 0.00 0.00 H ATOM 746 H2' ADE 275 10.796 -7.572 -0.583 1.00 0.00 H ATOM 747 H02' ADE 275 11.185 -9.606 0.454 0.00 0.00 H ATOM 748 H3' ADE 275 10.758 -6.282 1.534 0.00 0.00 H ATOM 749 P ADE 276 13.260 -7.257 1.977 0.00 65.98 P ATOM 750 OIP ADE 276 14.232 -7.912 2.879 0.00 66.78 O ATOM 751 02P ADE 276 13.062 -5.798 2.130 0.00 66.40 0 ATOM 752 05' ADE 276 13.667 -7.554 0.476 0.00 67.08 0 ATOM 753 C5' ADE 276 13.989 -8.893 0.110 0.00 68.35 c ATOM 754 C4' ADE 276 13.964 -9.087 -1.415 0.00 69.57 c ATOM 755 04' ADE 276 12.697 -8.626 -1.991 0.00 69.86 0 ATOM 756 Cl' ADE 276 12.956 -7.921 -3.216 0.00 70.40 c ATOM 757 C5 ADE 276 12.348 -4.304 -3.534 0.00 0.00 c ATOM 758 N7 ADE 276 12.161 -4.442 -2.189 0.00 0.00 N ATOM 759 C8 ADE 276 12.359 -5.715 -1.963 0.00 0.00 c ATOM 760 N9 ADE 276 12.653 -6.461 -3.074 0.00 0.00 N ATOM 761 Nl ADE 276 12.512 -3.357 -5.671 0.00 0.00 N ATOM 762 C2 ADE 276 12.790 -4.586 -6.118 0.00 0.00 C ATOM 763 N3 ADE 276 12.882 -5.735 -5.442 0.00 0.00 N ATOM 764 C4 ADE 276 12.648 -5.525 -4.125 0.00 0.00 C ATOM 765 C6 ADE 276 12.270 -3.151 -4.337 0.00 0.00 C ATOM 766 N6 ADE 276 11.964 -1.949 -3.763 0.00 0.00 N ATOM 767 C2' ADE 276 14.429 -8.212 -3.550 0.00 70.33 C ATOM 768 02' ADE 276 14.557 -9.452 -4.242 0.0Q 70.22 O ATOM 769 C3' ADE 276 15.016 -8.270 -2.146 0.00 70.19 C ATOM 770 03' ADE 276 16.305 -8.883 -2.131 0.00 71.00 0 ATOM 771 1H5' ADE 276 13.269 -9.616 0.558 0.00 0.00 H ATOM 772 2H5' ADE 276 15.006 -9.145 0.485 0.00 0.00 H ATOM 773 H4' ADE 276 14.062 -10.166 -1.665 0.00 0.00 H ATOM 774 HI' ADE 276 12.291 -8.358 -3.992 0.00 0.00 H ATOM 775 H8 ADE 276 12.313 -6.193 -0.991 0.00 0.00 H ER EC EC EC EC EC C M O O O O O O O Z O S O S Z O O O S U O O O O EC EC EQ EC EC r-C EC EC EC EC EC fe o ro r— in c ω iD ci in cri co iD c cn iD O -i '. LD -O CO O O rH r- rO LD CO CO LO rH CM .— LO CM CM CM rH o o o cD O O o en o o cn cn r— r— r— r— r— t— r— t— r— r- r— Lo r— r— z> o o o o o o O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O r H O O O O O O O O O O O O O O O O O O O O O O o α 3 ιn cM c^ ω ω co ω ' ^ H ιn H H s l cn ' . co H -l o ιη c l cl t . ω '. ιD ' q | c^l co ιn ^ ω co c^ι ^ r r— LD LD CM O cn cn ^r' r— cn ro o rH ^r co r— m m cϊ ^ n ω co H H ιn ^ ^ co w ι- o^ o c^| ιo r ^ cD c l Cfl Cn ^ ιn c co ω o ^ co ιn c O ιn r^ co r— o e H co ro co ^r CM Γ— m co m Lo ro cD ^r m H n H O -) N ω o l -l o ω l c^l H ιn ri H cι o o ^o ro c■ ιo ιn m co o cJl ^D ^ o ιo c o ^ ^ LO LD rO m r— ro m rH rH CM O O CO rH rH O rO m LD r— o CM ro ■ » CO CO "C CO N ■ !, O rH rH CM -0 l! 0 ^r ^r <-r m in in co cM ^ ^ co ^ •-r m m m -^ eo cM CM rH o o o rH I I I I I I I I I I I I 1 1 1 1 1 1 1 1 1 1 1 1 I I I I I I I I I I I I I I I I I I I cM rH H ^ι , m t— • co r— r- co r— LO LD m m m ^j' ^ ^ T m m r— r— co cn r— c cD -o ^ - ^r - r— co co o cM O O O o cn co co co co r— r— r— r— r— r— r— co o rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH rH i-H rH rH rH rH rH rH rH CM CM C^ ! LO LO LD LD LD Lo r— t- - r- r— r- r— r— r— r— r— r— r— r— r— r- r— ^ f^ ^ co co co ω co co ω co co co co co co co ∞ cυ ι^ c- OD CD r— r— r— r— r— t r— r— i i — i — r— r— r— r— r— r— r— r— r— i — r— r— r— t — r— r— r— r— r— r— r— i — ι — r— r— r— r— r— t — r— r— r— r— r— r— r— r— r— r— r— t— r— t — r— r— r— r— r— r— CM CM CM CM CM CM CM CM CM CM CM C Ovl CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM C CM CM CM CM CM CM CM CM CM CM CM C^ w S ωtS ωH iH-q ωH ωS p -C! Q Q Q Q O a C PC PC PC C CMM LLDD LLDD -- -- - C CMM CCMM CCMM -- —- r m c *-.ι rH i r rsi iDn iLnD - in r i —- - EEj EC. EC CM CM ro rH C m m Z Z I-S O Z CM rH CM EC O EC O O O O O EC r- LO r- co en o rH CM ro -sr Lo r— co e o rH C Co ^Φ -o Lo r— ω σi o H w cn '. in iD r- co c o H cN cη ^ in MD m o H CM cTϊ m iO h co cn o H M r si' in I— r— r— t— CO CO CD CD CO CO CO eO CXl CD e-^ CTl CTl Cn cn CΛ Cn Cn CΛ Cn O O O CD O O O O O O rH rH rH rH rH cH rH rH LO t— ■ r— r— r— r— r— r— r— r— r— r— - r— r— r— r— - r— r— r— r- - r— cD a> ω cD co ω ω eo ω ω cD ω ω co ω co co co co ω ω ω co co co ω co ro co co co co co co co © o 222222222222222222222222222222222222222222222222222222222222 O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O -H H -H -H H rH EH H - H -H H B EH EH EH H H -H -H H EH -H H rjH H H -H - H -H -H H EH EH -H -H H EH EH H H rH PC P C PC P P P P C P P P C P P P C P P P PC PC C PC P P P P PC C PC PC C PC C ^ ATOM 836 02' GUA 278 20.256 2.438 -5.816 0.00 68.72 0 ATOM 837 C3' GUA 278 21. 242 0. 454 -4. 775 0. 00 69. 09 c ATOM 838 03' GUA 278 22. 497 0. 851 -5. 328 0. 00 67. 95 0 ATOM 839 1H5' GUA 278 20. 480 -2. 533 -6. 390 0. 00 0. 00 H ATOM 840 2H5' GUA 278 22. 084 -1. 962 -5. 795 0. 00 0. 00 H ATOM 841 H4' GUA 278 20. 588 -0. 137 -6. 765 0. 00 0. 00 H ATOM 842 HI' GUA 278 18. ,106 1. ,418 -5. 003 0. 00 0. 00 H ATOM 843 HI GUA 278 17. ,140 3. ,141 0. 889 0. 00 0. 00 H ATOM 844 1H2 GUA 278 18. ,045 5. ,349 -1. 622 0. 00 0. 00 H ATOM 845 2H2 GUA 278 17. 518 5. 104 0. 013 0. 00 0. 00 H ATOM 846 H8 GUA 278 18. 618 -1. 646 -3. 111 0. 00 0. 00 H ATOM 847 H2' GUA 278 20. 410 2. 243 -3. 781 1. 00 0. 00 H ATOM 848 H02' GUA 278 21. 182 2. 545 -6. 046 0. 00 0. 00 H ATOM 849 H3' GUA 278 21. ,341 -0. ,029 -3. ,772 0. 00 0. 00 H ATOM 850 P CYT 279 23. ,801 0. ,823 -4. 434 0. 00 67. 53 P ATOM 851 OIP CYT 279 24. ,970 1. ,139 -5. 285 0. 00 67. 77 O ATOM 852 02P CYT 279 23. ,841 -0. ,438 -3. ,662 0. 00 67. ,32 O ATOM 853 05' CYT 279 23. ,551 2. ,024 -3. ,435 0. 00 66. ,23 O ATOM 854 C5' CYT 279 23. .646 3. .350 -3. ,943 0. ,00 64. .14 C ATOM 855 C4' CYT 279 23. ,230 4. .387 -2. ,891 0. 00 63. ,21 C ATOM 856 04' CYT 279 21. ,827 4. ,236 -2. ,510 0. 00 62. ,79 0 ATOM 857 Cl' CYT 279 21. ,682 4. .467 -1. ,096 0. ,00 61. ,93 C ATOM 858 Nl CYT 279 21. .161 3. .248 -0. .383 0. ,00 61. .38 N ATOM 859 C6 CYT 279 21. .290 1. .947 -0. .862 0. ,00 60, .69 C ATOM 860 C2 CYT 279 20, .640 3. .449 0, .941 0, .00 61 .58 C ATOM 861 02 CYT 279 20, .486 4 .592 1 .413 0, .00 62 .27 O ATOM 862 N3 CYT 279 20, .308 2 .339 1 .689 0, .00 61 .09 N ATOM 863 C4 CYT 279 20 .441 1, .078 1 .201 0, .00 60 .36 C ATOM 864 N4 CYT 279 20 .096 -0. .014 1 .942 0. .00 59 .29 N ATOM 865 C5 CYT 279 20 .951 0 .873 -0 .132 0. .00 60 .20 C ATOM 866 C2' CYT 279 23, .066 .948 -0 .597 0, .00 61 .93 C ATOM 867 02' CYT 279 23 .159 6 .369 -0, .688 0, .00 61 .54 O ATOM 868 C3' CYT 279 23 .980 4 .239 -1 .582 0 .00 62 .38 C ATOM 869 03' CYT 279 25 .295 4 .782 -1 .650 0 .00 62 .18 O ATOM 870 1H5' CYT 279 22 .997 3 .478 -4 .841 0 .00 0 .00 H ATOM 871 2H5' CYT 279 24 .698 3 .559 -4 .245 0 .00 0 .00 H ATOM 872 H4' CYT 279 23 .339 5 .414 -3 .302 0 .00 0 .00 H ATOM 873 HI' CYT 279 20 .938 5 .288 -0 .997 0 .00 0 .00 H ATOM 874 H6 CYT 279 21 .659 1 .838 -1 .876 0 .00 0 .00 H ATOM 875 1H4 CYT 279 19 .716 0 .115 2 .859 0 .00 0 .00 H ATOM 876 2H4 CYT 279 20 .177 -0 .932 1 .555 0 .00 0 .00 H ATOM 877 H5 CYT 279 21 .039 -0 .138 -0 .533 0 .00 0 .00 H ATOM 878 H2' CYT 279 23 .216 4 .655 0 .442 1 .00 0 .00 H ATOM 879 H02' CYT 279 23 .124 6 .573 -1 .625 0 .00 0 .00 H ATOM 880 H3' CYT 279 24 .056 3 .167 -1 .290 0 .00 0 .00 H ATOM 881 H03' CYT 279 25 .775 4 .228 -2 .272 0 .00 0 .00 H END

Claims: CLAIMS 1. An to silico method for identifying a compound that interacts with sub-domain Hid of the hepatitis C virus IRES, comprising the steps of: (a) providing atomic co-ordinates of said sub-domain Hid in a storage medium on a computer; and (b) using said computer to apply molecular modelling techniques to said co-ordinates. 2. The method 'of claim 1, wherein the atomic co-ordinates are iiid_gc .pdb or ιιid_gu . pdb, or variants thereof. 3. The method of claim 1, wherein the atomic co-ordinates are those of (i) G256, A257, G258, U259, A260, G273, A274, A275, A276 and/or (ii) U264, U265. G266, G267, G268, U269, of IIId_gc .pdb or IIId_gu.pdb. 4. The method of any preceding claim, wherein the molecular modelling techniques involve de novo compound design. 5. The method of claim 4, wherein the de novo compound design involves (i) the identification of functional groups or small molecule fragments which can interact with sites in the binding surface of sub-domain Hid, and (ii) linking these in a single compound 6. The method of any one of claims 1 to 3, wherein the molecular modelling techniques use a pharmacophore of sub-domain Illd. 7. The method of any one of claims 1 to 3, wherein the molecular modelling techniques use automated docking algorithms. 8. The method of any preceding claim, wherein the compound is a reporter molecule for use in an assay for displacement from a fragment of the HCV IRES. 9. The method of claim 8, wherein the reporter molecule is a peptide, a small organic molecule, an oligonucleotide, or a PNA. 10. The method of any preceding claim, comprising the steps of: (c) providing a compound identified by said molecular modelling techniques; and (d) contacting said compound with the HCV IRES and assaying the interaction between them. 11. A compound identified using the method of any preceding claim. 12. A computer-readable medium for a computer, characterised in that the medium contains atomic co-ordinates of the sub-domain Hid of the hepatitis C virus IRES. 13. The medium of claim 10, wherein the atomic co-ordinates are ιιid_gc.pdb or in d_gu . pdb, or variants thereof. 14. An assay for displacement from a fragment of the HCV IRES, wherein the assay utilises a reporter molecule identified using the method of claim 8 or claim 9.

Inventors: ABOUL-ELA FAREED, AFSHAR MOHAMMAD, COLLIER ADAM, KLINCK ROSCOE, WALKER STEPHEN, WESTHOF ERIC, ABOUL-ELA, FAREED, AFSHAR, MOHAMMAD, COLLIER, ADAM, KLINCK, ROSCOE, WALKER, STEPHEN, WESTHOF, ERIC
Applicants: ABOUL ELA FAREED, AFSHAR MOHAMMAD, COLLIER ADAM, KLINCK ROSCOE, RIBOTARGETS LTD, WALKER STEPHEN, WESTHOF ERIC, ABOUL-ELA, FAREED, AFSHAR, MOHAMMAD, COLLIER, ADAM, KLINCK, ROSCOE, RIBOTARGETS LIMITED, WALKER, STEPHEN, WESTHOF, ERIC
Application year: 2001
Main classification: C12Q1
IPC codes: C12Q1, G01N33, G06F19