bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relaxed potential energy surfaces of maltose
Authors: Tran Vinh , Buleon Alain , Imberty Anne , Perez Serge 
Published: December 2004

AbstractExperimentally observed solution conformations of carbohydrate molecules might correspond to a dynamical average of several interconverting conformers in solution. In order to understand and describe more precisely molecular flexibility and motions, new computational routes have to be envisaged. Compared to conventional approaches where sugar residues are treated as rigid, the optimization of all the internal parameters—i.e., bond angles, valence angles, and all torsional angles—is an important step toward more realistic information. Here we report the calculations of potential energy surfaces where all the internal coordinates of the molecules were “relaxed” and minimized through an extensive molecular mechanics scheme. For this work, a prototypical carbohydrate system, the disaccharide α‐maltose, was selected. The inclusion of the relaxed principle into conformational description of maltose does not generally alter the overall shape of the allowed low‐energy regions, or the position of the local minima. However, flexibility within the ring plays a crucial role. Its principle effect is the lowering of energy barriers to conformational transitions about the glycosidic bonds, permitting pathways among the low‐energy minima. This occurs with retaining the overall 4C1 conformation of the glucose residues. The torsional angles corresponding to the orientations of the hydroxyl groups, especially the primary hydroxyl ones, display stable arrangements separated by energy barriers. They create subpopulations of stable conformers and it has not been possible to take into consideration interconversion of one subpopulation to another one. A “synthetic” relaxed potential energy surface is proposed, which can provide a realistic starting base for further investigation of solution behavior of dynamic simulations.
Association kinetics of site‐specific protein‐DNA interactions: Roles of nonspecific DNA sites and of the molecular location of the specific site
Authors: Mazur Sharlyn J. , Record M. Thomas 
Published: December 2004

AbstractWe have applied the formalism developed previously for the kinetics of domain‐localized reaction [S. Mazur and M. T. Record, Jr. (1986) Biopolymers 25, 985–1008] to describe complex mechanisms of association of a protein with a specific site on a large DNA molecule also containing many nonspecific binding sites. These nonspecific sites participate in the mechanism of formation of the specific complex through competitive binding and the facilitating mechanisms of sliding and transfer. The effects of localizing the sites in a domain are represented by a simple algebraic expression, and the sequence of interactions within the domain are described by equations closely related to a conventional, homogeneous solution mechanism. We apply this formalism to examine the interplay between sliding and direct transfer in domain‐localized interactions in general and in the lac repressor‐lac operator interaction in particular. Experimental investigation of the effect of the molecular location of the specific site (e.g., end vs middle of the polymer chain) on the kinetics of association may allow the contributions of sliding and direct transfer to be resolved.
Monte carlo studies on equilibrium globular protein folding. II. β‐barrel globular protein models
Authors: Skolnick Jeffrey , Kolinski Andrzej , Yaris Robert 
Published: December 2004

AbstractIn the context of dynamic Monte Carlo simulations on a model protein confined to a tetrahedral lattice, the interplay of protein size and tertiary structure, and the requirements for an all‐or‐none transition to a unique native state, are investigated. Small model proteins having a primary sequence consisting of a central bend neutral region flanked by two tails having an alternating hydrophobic/hydrophilic pattern of residues are seen to undergo a continuous transition to a β‐hairpin collapsed state. On increasing the length of the tails, the β‐hairpin structural motif is found to be in equilibrium with a four‐member β‐barrel. Further increase of the tail length results in the shift of the structural equilibrium to the four‐member β‐barrel. The random coil to β‐barrel transition is of an all‐or‐none character, but while the central turn is always the desired native bend, the location of the turns involving the two external strands is variable. That is, β‐barrels having the external stands that are two residues out of register are also observed in the transition region. Introduction into the primary sequence of two additional regions that are at the very least neutral toward turn formation produces an all‐or‐none transition to the unique, native, four‐member β‐barrel. Various factors that can augment the stability of the native conformation are explored. Overall, these folding simulations strongly indicate that the general rules of globular protein folding are rather robust—namely, one requires a general pattern of hydrophobic/hydrophilic residues that allow the protein to have a welldefined interior and exterior and the presence of regions in the amino acid sequence that at the very least are locally indifferent to turn formation. Since no site‐specific interactions between hydrophobic and hydrophilic residues are required to produce a unique four‐member β‐barrel, these simulations strongly suggest that site specificity is involved in structural fine‐tuning.
Monte carlo studies on equilibrium globular protein folding. III. The four helix bundle
Authors: Sikorski Andrzej , Skolnick Jeffrey 
Published: December 2004

AbstractThe nature of the equilibrium conformational transition from the denatured state to a four‐member α‐helical bundle was studied employing a dynamic Monte Carlo algorithm in which the model protein chain was confined to a tetrahedral lattice. The model chain was allowed to hunt over all phase space, the target native state was not assumed a priori, and no site‐specific interactions were introduced. The exterior vs the interior part of the protein is distinguished by the pattern of hydrophilic and hydrophobic interactions encoded into the primary sequence. The importance of a statistical preference for forming bends, as a function of bend location in the primary sequence, and helical wheel type cooperative interactions were examined, and the necessary conditions for collapse of the chain to the unique native structure were investigated. It was found that an amphipathic pattern of hydrophobic/hydrophilic interactions along with a statistical preference of the central residues for bend formation are sufficient to obtain the four‐helix bundle. The transition to the native state has an all‐or‐none character.
Solvation thermodynamics of biopolymers. I. Separation of the volume and surface interactions with estimates for proteins
Authors: Ben‐Naim A. , Ting K.‐L. , Jernigan R. L. 
Published: December 2004

AbstractThe present paper is a systematic first approach to the problem of solvation thermodynamics of biomolecules.Most previous approaches have been only crude estimates of solvent contributions, and have simply assessed solvation free energy as proportional to surface areas.Here we estimate the various contributions and divide them into (a) hard‐core interactions dependent upon the entire volume of solute and (b) the remainder of interactions manifested through surfaces, such as van der Waals, charge—charge, or hydrogen bonds. We have estimated the work to create a cavity with scaled‐particle theory (SPT), the van der Waals interactions on the surface, and hydrogen bonds between the surface and the solvent. The conclusion here is that this latter term is the largest component of the solvation free energy of proteins.From estimates on nine diverse proteins, it is clear that the larger the protein, the more dominant is the hydrogen‐bond term. In the next paper, we indicate that correlations between hydrogen‐bonding groups on the surfaces could increase the magnitude of the hydrogen‐bond contribution.
The regulation of size and form in the assembly of collagen fibrils in vivo
Authors: Chapman John A. 
Published: December 2004

AbstractA possible mechanism for regulating the lateral growth of collagen fibrils in vivo is considered. A growth inhibitor associated with a particular part of the long semiflexible collagen molecule restricts that part of the molecule to the surface of the growing assembly. Lateral accretion ceases when these inhibitors form a complete circumferential layer around the fibril surface. Cell‐mediated removal of the inhibitors allows lateral growth to proceed to a second limiting layer, and so on to subsequent limiting layers. In this way, cycles of inhibitor removal and limited lateral accretion permit growth to be synchronized over large populations of fibrils. Observed diameter distributions in bundles of embryonic and neonatal fibrils are those expected from a mechanism of this kind. The mechanism depends on the existence of axial order (D‐periodicity) in fibrils, but not on any specific lateral packing of molecules. Rather, contacts between newly assembled molecules are presumed to be partly fluid‐like in lateral directions (except where covalent cross‐links have formed). Some initial fluidity in lateral packing prior to cross‐linking does not preclude the subsequent emergence of quasi‐crystalline packing as cross‐links form. The cylindrical shape of fibrils in vivo may also be attributable in part to fluidity of intermolecular contacts at the growing surface.
Electric dichroism and bending amplitudes of DNA fragments according to a simple orientation function for weakly bent rods
Authors: Porschke Dietmar 
Published: December 2004

AbstractThe linear dichroism is calculated for DNA fragments in their thermal bending equilibrium. These calculations are given for relatively short fragments, where bent molecules can be described by an arc model. Using the measured value of 350 Å for the persistence length, the limit dichroism (corresponding to complete alignment) decreases due to thermal bending, e.g., for a fragment with 100 base pairs to 80% of the value expected for straight molecules. Thermal bending should lead to a strong continuous decrease of the dichroism with increasing chain length, which is not observed, however, in electric dichroism experiments due to electric stretching. The influence of the electric field on the bending equilibrium is described by a contribution to the bending energy, which is calculated from the movement of charge equivalents against the potential gradient upon bending. The charge equivalents, which are assigned to the helix ends, are derived from the dipole moments causing the stationary degree of orientation. By this procedure the energy term inducing DNA stretching is given for induced, permanent, and saturating induced dipole models without introduction of any additional parameter. The stationary dichroism at a given electric field strength is then calculated according to an arc model by integration over all angles of orientation of helix axes or chords with respect to the field vector, and at each of these angles the contribution to the dichroism is calculated by integration over all helices with different degrees of bending. Orientation functions obtained by this procedure are fitted to dichroism data measured for various restriction fragments. Optimal fits are found for an induced dipole model with saturation of the polarizability. The difference between orientation functions with and without electric stretching is used to evaluate dichroism bending amplitudes. Both chain length and field strength dependence of bending amplitudes are consistent with experimental amplitudes derived from the dichroism decay in low salt buffers containing multivalent ions like Mg2+, spermine, or [(CoNH3)6]3+. Bending amplitudes can be used to evaluate the persistence length from electrooptical data obtained for a single DNA restriction fragment. Bending and stretching effects are considerable already at relatively low chain length, and thus should not be neglected in any quantitative evaluation of experimental data.
Inverted repeat sequences can influence the melting transitions of linear DNAs
Authors: McCampbell Charles R. , Wartell Roger M. , Plaskon R. Richard 
Published: December 2004

AbstractThe influence of inverted repeat sequences on the melting transitions of linear of DNAs has been examined. Derivative melting curves (DMC) of a 514 base pair (bp) DNA, seven subfragments of this DNA, and four other DNAs have been compared to predictions of DNA melting theory. The 514‐bp DNA contains three inverted repeat sequences that can form cruciform structures in supercoiled DNA. We refer to these sequences as c‐inverted repeats. Previous work showed that the DMC of this DNA, unlike a number of other DNAs, is not accurately predicted by DNA melting theory. Since the theoretical model does not include hairpin‐like structures, it was suggested that hairpin or cruciform formation in these inverted repeats may be responsible for this discrepancy. Our results support this hypothesis. Predicted DMCs are in good agreement with DNAs with no inverted repeats, or inverted repeats not evident in supercoiled DNA. Differences between the theoretical and experimental Tm's are ≤ 0.3°C. DNA molecules that contain one or more of the three c‐inverted repeats are not as accurately predicted. Experimental Tm values are lower than predicted values by 0.7–3.8°C. It is concluded that some inverted repeat sequences can form hairpin‐like structures during the melting of linear DNAs. These structures appear to lower overall DNA stability.
The influence of the side‐chain sequence on the structure–activity correlations of immunomodulatory branched polypeptides. Synthesis and conformational analysis of new model polypeptides
Authors: Mező G. , Hudecz F. , Kajtár J. , Szókán Gy. , Szekerke M. 
Published: December 2004

AbstractNew branched polypeptides were synthesized for a detailed study of the influence of the side‐chain structure on the conformation and biological properties. The first subset of polypeptides were prepared by coupling of tetrapeptides to poly[L‐Lys]. These polymers contain either DL‐Ala3‐X {poly[Lys‐(X‐DL‐Ala3)n]} X‐DL‐Ala3 {poly[Lys‐(DL‐Ala3‐X)n] (n ≤ 1)} tetrapeptide side chains. Another group of branched polymers comprise a mixture of DL‐Alam and of DL‐Alam‐X oligomeric branches in a random distribution {poly[Lys‐(DL‐Alam‐Xi)](i < 1, m ∼ 3)}. In each subset the X = Leu or Phe derivatives were prepared.The N‐protected tetrapeptides were synthesized by conventional liquid phase methods and were coupled as active esters. The degree of racemization was found relatively high both for active esters and coupled derivatives, when optically active amino acids were in the C‐terminal position of the tetrapeptides. In the case of the poly[Lys‐(Leu‐DL‐Ala3)n] derivative, comparative experiments were carred out using various methodical alterations. The highest stereochemical homogeniety could be achieved when the tetrapeptide active ester was synthesized by the “backing off” method.CD spectra of poly[Lys‐(Xi‐DL‐Alam)] (i < 1, m ∼ 3) and of poly[Lys‐(X‐DL‐Ala3)n] were analyzed and compared to those of poly[Lys‐(DL‐Ala3‐Xi)] and of poly[Lys‐(DL‐Ala3‐X)n]. All measurements were performed in water solutions of varying pH values and ionic strengths. The data obtained suggest that branched polypeptides containing a mixture of two different types of oligomeric side chains (DL‐Alam and DL‐Alam‐Xi or Xi‐DL‐Alam) distributed randomly adopt an almost indentical conformation to those that comprise only the respective tetrapeptide (DL‐Ala3‐X or X‐DL‐Ala3) branches. The results also indicate that the tendency to form an ordered structure is determined by the indentity and the position of the chiral amino acid X (Phe or Leu) in the side chain.
Vibrational free energy, entropy, and temperature factors of DNA calculated by a helix lattice approach
Authors: Girirajan K. S. , Young L. , Prohofsky E. W. 
Published: December 2004

AbstractThe vibrational contribution to the free energy, entropy, and the temperature factors of the different atoms in the unit cell are calculated using the method of helix lattice dynamics for the DNA homopolymer poly(dG · poly(dC)) in the B conformation. These results are compared to other theoretical calculations and the temperature (B) factors are compared to experiment as well. The problems encountered in using small molecule approximations to describe B factors in DNA like long chain molecules are discussed and a corrected estimate of the temperature factors are presented. Significant differences are found between the different theoretical approaches as reflected in the results of temperature factor calculations.
I – V characteristics and electrical conductivity of synthetic melanin
Authors: Osak Władysław , Tkacz Katarzyna , Czternastek Halina , SłAwiński Janusz 
Published: December 2004

AbstractI – V characteristics for synthetic melanin were investigated at – 10 and 25°C. It was found that the Ohm law is valid for low voltages whereas the Child law holds for higher ones. Furthermore, the steady state electrical conductivity was estimated. The change of activation energy from 0.76 eV for low temperatures to 1.58 eV was noticeable near 0°C.
Vibrational CD studies of the solution conformation of simple alanyl peptides as a function of pH
Authors: Zuk William M. , Freedman Teresa B. , Nafie Laurence A. 
Published: December 2004

AbstractThe CH‐stretching vibrational CD (VCD) spectra of glycyl‐L‐alanine, L‐alanylglycine, and L‐alanyl‐L‐alanine have been studied at neutral, high, and low pH in D2O solution. The intense positive VCD band attributed to the CαH stretch of the alanyl residue in glycyl‐L‐alanine at neutral pH is absent in L‐alanylglycine. In contrast to the VCD spectra of L‐alanine, the positive methine‐stretching VCD band in glycyl‐L‐alanine and L‐alanyl‐L‐alanine is still present at pH 2. Based on the ring current mechanism, the VCD spectra are consistent with the presence of a five‐membered CO … HN intramolecular hydrogen‐bonded ring between the C‐terminal carboxylate and peptide NH groups at neutral and high pH, and a seven‐membered COH … OC hydrogen‐bonded ring between the C‐terminal carboxyl OH and peptide CO groups at low pH. In the N‐terminal alanyl residue, the peptide CO group is hydrogen bonded to the NH trans to the methine bond. The CH‐stretching VCD spectra of L‐alanyl‐L‐alanyl‐L‐alanine at neutral pH are consistent with two intramolecularly hydrogen‐bonded conformations for the central alanyl residue.
Interactions of nucleic acids with distamycins. The drug monomeric chromophore
Authors: Forni A. , Moretti I. , Torre G. , Marconi G. , Samori B. 
Published: December 2004

AbstractA study of the monomeric chromophore of the oligopeptides netropsin (1), distamycin III (2), and distamycin V (3) by polarization spectroscopy techniques1 and molecular orbital calculations is reported. Linear dichroism spectra of the monomeric model compounds 1‐methyl‐2(ethylcarbamoyl)‐4‐acetamido‐pyrrole (4) and 1‐methyl‐2(ethylcarbamoyl)‐pyrrole (5) dissolved and oriented in lyotropic and thermotropic liquid crystals provide, together with the magnetic CD spectra, experimental checks of the theoretical calculations. The polarization directions of the investigated transition obtained by these means in this study allow us to build up in the following paper2 the exciton states of (1)‐(3) and these provide a stereochemical interpretation of the flow linear dichroism spectra of the complexes of DNA with (2) and (3).
Side‐chain interactions in the C‐peptide helix: Phe 8 ⃛ His 12+
Authors: Shoemaker Kevin R. , Fairman Robert , Schultz David A. , Robertson Andrew D. , York Eunice J. , Stewart John M. , Baldwin Robert L. 
Published: December 2004

AbstractPrevious studies have demonstrated that His 12 plays a major role in the pH‐dependent stability of the helix formed by the isolated C‐peptide (residues 1–13 of ribonuclease A). Here, amino acid replacement experiments show that His 12+ stabilizes the C‐peptide helix chiefly by interacting with Phe 8. The Phe 8 ⃛ His 12+ ring interaction is specific for the protonated form of His 12 (His 12+) and the interaction is not screened significantly by NaCl, unlike the charged group ⃛ helix dipole interactions studied earlier in C‐peptide. Analogs of C‐peptide that are unable to form the Phe 8 ⃛ His 12+ interaction show large increases in helix content for Phe → Ala and His → Ala. Therefore, the helical tendencies of the individual residues Phe, His, and Ala are important in determining the result of a replacement experiment. Since the side chains of Phe 8 and His 12 probably interact within the N‐terminal helix of ribonuclease A, the existence of the Phe 8 ⃛ His 12+ interaction in the isolated C‐peptide helix adds to the evidence that the C‐peptide helix is an autonomous folding unit.
Synthesis of analogues of peptide YY with modified N‐terminal regions: Relationships of amphiphilic secondary structures and activity in rat vas deferens
Authors: Minakata Hiroyuki , Iwashita Takashi 
Published: December 2004

AbstractPeptide YY (PYY) not only has distinct sequence homology with neuropeptide Y (NPY) and avian pancreatic polypeptide (APP), but it also exhibits both NPY‐ and APP‐like biological activities. We synthesized two analogues of PYY, A1 and A2, with modified N‐terminal regions, and compared their chemical and biological properties to those of PYY and the C‐terminal fragment of PYY, (13–36)PYY. This study shows that there is a good correlation between the stability of amphiphilic α‐helical structure and the biological activity of these peptides. A CD study of (13–36)PYY in mixed H2O and trifluoroethanol (TFE) solutions indicated a significant increase in α‐helical segments (26–79%) with increasing TFE proportions. Since the fragment (13–36)PYY had potent activity in the rat vas deferens (RVD) assay, the secondary structure is possibly required on the RVD cell surface receptors. The analogues, A1 and A2, were designed to increase the stability of the α‐helical structures by incorporation of modified N‐terminal regions. The CD studies, and the RVD assays of A1 and A2, suggest that the amphiphilic α‐helical structures are stabilized by intramolecular hydrophobic interactions with the N‐terminal regions and/or by intermolecular hydrophobic interactions in the self‐association process, and subsequently potentiate the activities of the peptides compared to those of PYY and (13–36)PYY.
Conformationally constrained α‐helical peptide models for protein ion channels
Authors: DeGrado W. F. , Lear J. D. 
Published: December 2004

AbstractRecently we described the design, synthesis, and characterization of some simple amphiphilic α‐helical models for protein ion channels. These peptides, composed of only Leu and Ser residues, are hypothesized to form helical bundles capable of passing ions across phospholipid bilayers. In an effort to demonstrate that the peptides are, in fact, helical in their active ion‐conducting state, the conformationally constrained amino acid, Cα, Cα‐dimethylglycine (α‐aminoisobutyric acid, Aib), was introduced simulataneously at three positions into one of the model peptides, H2N‐(Leu‐Ser‐Leu‐Leu‐Leu‐Ser‐Leu)3‐CONH2, giving H2N‐(Leu‐Ser‐Leu‐Aib‐Leu‐Ser‐Leu)3‐CONH2. Examination of a tetrameric model for the channel suggested that this substitution should have a minimal effect on conductance. CD spectroscopy of the Aib‐modified and original peptide in phospholipid vesicles indicated that both were highly α‐helical. Furthermore, the Aib‐containing peptide formed proton channels nearly identical in conductance to the original peptide.