bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic pKas of ionizable residues in proteins: An explicit solvent calculation for lysozyme
Authors: Del Buono Gabriela S. , Figueirido Francisco E. , Levy Ronald M. 
Published: May 2005

AbstractMolecular dynamics simulations of triclinic hen egg white lysozyme in aqueous solution were performed to calculate the intrinsic pKas of 14 ionizable residues. An all‐atom model was used for both solvent and solute, and a single 180 ps simulation in conjunction with a Gaussian fluctuation analysis method was used. An advantage of the Gaussian fluctuation method is that it only requires a single simulation of the system in a reference state to calculate all the pKas in the protein, in contrast to multiple simulations for the free energy perturbation method. pKint shifts with respect to reference titratable residues were evaluated and compared to results obtained using a finite difference Poisson‐Boltzmann (FDPB) method with a continuum solvent model; overall agreement with the direction of the shifts was generally observed, though the magnitude of the shifts was typically larger with the explicit solvent model. The contribution of the first solvation shell to the total charging free energies of the titratable groups was explicitly evaluated and found to be significant. Dielectric shielding between pairs of titratable groups was examined and found to be smaller than expected. The effect of the approximations used to treat the long‐range interactions on the pKint shifts is discussed. © 1994 Wiley‐Liss, Inc.
Helix packing in proteins: Prediction and energetic analysis of dimeric, trimeric, and tetrameric GCN4 coiled coil structures
Authors: Delano Warren L. , Brünger Axel T. 
Published: May 2005

AbstractA simulated annealing method for atomic resolution structure prediction of α‐helical coiled coil proteins is described which draws upon knowledge of the oligomerization state, the helix directionality, and the properties of heptad repeat sequences. Unknown structural parameters, such as the coiled coil twist angle and the side chain conformations, are heavily sampled while allowing for flexibility in the helix backbone geometry. Structures of the wild‐type GCN4 dimer [O'Shea et al., Science 254:539–544, 1991] and a mutant tetramer [Harbury et al., Science 292:1401–1407, 1993] have been generated and compared with the X‐ray crystal structures. The wild‐type dimer model has a root mean square coordinate deviation from the crystal structure of 0.73 Å for nonhydrogen atoms in the dimerization interface. Structures of a mutant dimer and a mutant trimer have been predicted. Packing energetics were analyzed for core leucine and isoleucine side chains in dimeric and tetrameric coiled coils. Strong packing preferences were found in the dimers but not in the tetramers. Thus, packing in the dimer may be responsible for the switch from a two‐stranded to a four‐stranded coiled coil caused by the GCN4 leucine zipper mutations. © 1994 Wiley‐Liss, Inc.
Learning about protein folding via potential functions
Authors: Maiorov V. N. , Crippen G. M. 
Published: May 2005

AbstractOver the last few years we have developed an empirical potential function that solves the protein structure recognition problem: given the sequence for an n‐residue globular protein and a collection of plausible protein conformations, including the native conformation for that sequence, identify the correct, native conformation. Having determined this potential on the basis of only some 6500 native/nonnative pairs of structures for 58 proteins, we find it recognizes the native conformation for essentially all compact, soluble, globular proteins having known native conformations in comparisons with 104 to 106 reasonable alternative conformations apiece. In this sense, the potential encodes nearly all the essential features of globular protein conformational preference. In addition it “knows” about many additional factors in protein folding, such as the stabilization of multimeric proteins, quaternary structure, the role of disulfide bridges and ligands, proproteins vs. processed proteins, and minimal strand lengths in globular proteins. Comparisons are made with other sorts of protein folding problems, and applications in protein conformational determination and prediction are discussed. © 1994 Wiley‐Liss, Inc.
Conformational analysis of hemopexin by fourier‐transform infrared and circular dichroism spectroscopy
Authors: Wu Ming‐Lei , Morgan William T. 
Published: May 2005

AbstractHemopexin is a serum glyco‐protein that binds heme with the highest known affinity of any characterized heme‐binding protein and plays an important role in receptormediated cellular heme uptake. Complete understanding of the function of hemopexin will require the elucidation of its molecular structure. Previous analysis of the secondary structure of hemopexin by far‐UV circular dichroism (CD) failed due to the unusual positive ellipticity of this protein at 233 nm. In this paper, we present an examination of the structure of hemopexin by both Fourier‐transform infrared (FTIR) and circular dichroism spectroscopy. Our studies show that hemopexin contains about 55% β‐structure, 15% α‐helix, and 20% turns. The two isolated structural domains of hemopexin each have secondary structures similar to hemopexin. Although there are significant tertiary conformational changes indicated by the CD spectra, the overall secondary structure of hemopexin is not affected by binding heme. However, moderate changes in secondary structure do occur when the heme‐binding domain of hemopexin associates with heme. In spite of the exceptionally tight binding at neutral pH, heme is released from the bis‐histidyl heme–hemopexin complex at pH 5.0. Under this acidic condition, hemopexin maintains the same overall secondary structure as the native protein and is able to resume the heme‐binding function and the native structure of the hemeprotein (as indicated by the CD spectra) when returned to neutral pH. We propose that the state of hemopexin identified in vitro at pH 5.0 resembles that of this protein in the acidic environment of the endosomes in vivo when hemopexin releases heme during receptor‐mediated endocytosis. © 1994 Wiley‐Liss, Inc.
Protein simulations using techniques suitable for very large systems: The cell multipole method for nonbond interactions and the Newton‐Euler inverse mass operator method for internal coordinate dynamics
Authors: Mathiowetz Alan M. , Jain Abhinandan , Karasawa Naoki , Goddard William A. 
Published: May 2005

AbstractTwo new methods developed for molecular dynamics simulations of very large proteins are applied to a series of proteins ranging up to the protein capsid of tomato bushy stunt virus (TBSV).For molecular dynamics of very large proteins and polymers, it is useful to carry out the dynamics using internal coordinates (say, torsions only) rather than Cartesian coordinates. This allows larger time steps, eliminates problems with the classical description of high energy modes, and focuses on the important degrees of freedom. The resulting equation of motion has the form

equation image

where for T is the vector of generalized forces, ℳ︁(θ) is the moments of inertia tensor, is the vector of torsions, and 𝒞 is a vector containing Coriolis forces and nonbond forces. The problem is that to calculate the acceleration vector from ℳ︁, 𝒞, and Trequires inverting. ℳ︁(θ), an order 𝒩3calculation. Since the number of degrees of freedom might be 300,000 for a million atom system, solving these equations every time step is impractical, restricting internal coordinate methods to small systems. The new method, Newton‐Euler Inverse Mass Operator (NEIMO) dynamics, constructs the torsional accelerations vector directly by an order 𝒩 process, allowing internal‐coordinate dynamics to be solved for super larger (million atom) systems, The first use of the NEIMO method for molecular dynamics of proteins is presented here.A second serious difficulty for large proteins is calculation of the nonbond forces. We report here the first application to proteins of the new Cell Multipole Method (CMM) to evaluate the Coulomb and van der Waals interactions. The cost of CMM scales linearly with the number of particles while retaining an accuracy significantly better than standard non bond methods (involving cutoffs).Results for NEIMO and CMM are given for simulations of a wide range of peptide and protein systems, including the protein capsid of TBSV with 488,000 atoms. The computational times for NEIMO and CMM are demonstrated to scale linearly with size. With NEIMO the dynamics time steps can be as large as 20 fs (for small peptides), much larger than possible with standard Cartesian coordinate dynamics.For TBSV we considered both the normal form and the high pH form, in which the Ca2+ ions are removed. These calculations lead to a contraction of the protein for both forms (probably because of ignoring the RNA core not observed in the X‐ray). © 1994 Wiley‐Liss, Inc.
Polar and nonpolar atomic environments in the protein core: Implications for folding and binding
Authors: Koehl Patrice , Delarue Marc 
Published: May 2005

AbstractHydrophobic interactions are believed to play an important role in protein folding and stability. Semi‐empirical attempts to estimate these interactions are usually based on a model of solvation, whose contribution to the stability of proteins is assumed to be proportional to the surface area buried upon folding. Here we propose an extension of this idea by defining an environment free energy that characterizes the environment of each atom of the protein, including solvent, polar or nonpolar atoms of the same protein or of another molecule that interacts with the protein. In our model, the difference of this environment free energy between the folded state and the unfolded (extended) state of a protein is shown to be proportional to the area buried by nonpolar atoms upon folding. General properties of this environment free energy are derived from statistical studies on a database of 82 well‐refined protein structures. This free energy is shown to be able to discriminate misfolded from correct structural models, to provide an estimate of the stabilization due to oligomerization, and to predict the stability of mutants in which hydrophobic residues have been substituted by site‐directed mutagenesis, provided that no large structural modifications occur. © 1994 Wiley‐Liss, Inc.
Crystallization and preliminary crystallographic analysis of the N‐terminal two domain fragment of vascular cell adhesion molecule‐1 (VCAM‐1)
Authors: Wang Jia‐huai , Pepinsky Blake , Karpusas Michael , Liu Jin‐huan , Osborn Laurelee 
Published: May 2005

AbstractA molecular fragment comprising the first two domains of the human vascular cell adhesion molecule‐l (VCAM‐l) has been crystallized by the vapor diffusion method. Two crystal forms have been examined by X‐ray analysis: One crystal form belongs to the space group C2 with two molecules in the asymmetric unit and cell parameters: a = 122.1 Å, b = 48.9 Å, c = 73.4 Å, and β = 117.4°. The other crystal form belongs to the space group P21 with one molecule in the asymmetric unit and cell parameters: a = 40.4 Å, b = 45.7 Å, c = 54.7 Å, and β = 100.5°. Diffraction data up to 1.9 Å resolution have been collected for the C2 crystal form. © 1994 Wiley‐Liss, Inc.
Homology models of two isozymes of manganese peroxidase: Prediction of a Mn(II) binding site
Authors: Johnson Forrester , Loew Gilda H. , Du Ping 
Published: May 2005

AbstractThe three‐dimensional structures of two isozymes of manganese peroxidase (MnP) have been predicted from homology modeling using lignin peroxidase as a template. Although highly homologous, MnP differs from LiP by the requirement of Mn(II) as an intermediate in its oxidation of substrates. The Mn(II) site is absent in LiP and unique to the MnP family of peroxidases. The model structures were used to identify the unique Mn(II) binding sites, to determine to what extent they were conserved in the two isozymes, and to provide insight into why this site is absent in LiP. For each isozyme of MnP, three candidate Mn(II) binding sites were identified. Energy optimizations of the three possible Mn(II) enzyme complexes allowed the selection of the most favorable Mn(II) binding site as one with the most anionic oxygen moieties best configured to act as ligands for the Mn(II). At the preferred site, the Mn(II) is coordinated to the carboxyl oxygens of Glu‐35, Glu‐39, and Asp‐179, and a propionate group of the heme. The predicted Mn(II) binding site is conserved in both isozymes. Comparison between the residues at this site in MnP and the corresponding residues in LiP shows that two of the three anionic residues in MnP are replaced by neutral residues in LiP, explaining why LiP does not bind Mn(II). © 1994 Wiley‐Liss, Inc.
Structural analysis of two crystal forms of lentil lectin at 1.8 Å resolution
Authors: Loris Remy , van Overberge David , Dao‐Thi Minh‐Hoa , Poortmans Freddy , Maene Norbert , Wyns Lode 
Published: May 2005

AbstractThe structures of two crystal forms of lentil lectin are determined and refined at high resolution. Orthorhombic lentil lectin is refined at 1.80 Å resolution to anR‐factor of 0.184 and monoclinic lentil lectin at 1.75 Å resolution to anR‐factor of 0.175. These two structures are compared to each other and to the other available legume lectin structures. The monosaccharide binding pocket of each lectin monomer contains a tightly bound phosphate ion. This phosphate makes hydrogen bonding contacts with Asp‐81β, Gly‐99β, and Asn‐125β, three residues that are highly conserved in most of the known legume lectin sequences and essential for monosaccharide recognition in all legume lectin crystal structures described thus far. A detailed analysis of the composition and properties of the hydrophobic contact network and hydrophobic nuclei in lentil lectin is presented. Contact map calculations reveal that dense clusters of nonpolar as well as polar side chains playa major role in secondary structure packing. This is illustrated by a large cluster of 24 mainly hydrophobic amino acids that is responsible for the majority of packing interactions between the two β‐sheets. Another series of four smaller and less hydrophobic clusters is found to mediate the packing of a number of loop structures upon the front sheet. A very dense, but not very conserved cluster is found to stabilize the transition metal binding site. The highly conserved and invariant nonpolar residues are distributed asymmetrically over the protein. © 1994 Wiley‐Liss, Inc.
Crystallization, molecular replacement solution, and refinement of tetrameric β‐amylase from sweet potato
Authors: Cheong Cheom Gil , Eom Soo Hyun , Chang Changsoo , Shin Dong Hae , Song Hyun Kyu , Min Kyeongsik , Moon Jin Ho , Kim Kyeong Kyu , Hwang Kwang Yeon , Suh Se Won 
Published: May 2005

AbstractSweet potato β‐amylase is a tetramer of identical subunits, which are arranged to exhibit 222 molecular symmetry. Its subunit consists of 498 amino acid residues (Mr 55,880). It has been crystallized at room temperature using polyethylene glycol 1500 as precipitant. The crystals, growing to dimensions of 0.4 mm × 0.4 mm × 1.0 mm within 2 weeks, belong to the tetragonal space group P42212 with unit cell dimensions of a = b = 129.63 Å and c = 68.42 Å. The asymmetric unit contains 1 subunit of β‐amylase, with a crystal volume per protein mass (VM) of 2.57 Å3/Da and a solvent content of 52% by volume. The three‐dimensional structure of the tetrameric β‐amylase from sweet potato has been determined by molecular replacement methods using the monomeric structure of soybean enzyme as the starting model. The refined subunit model contains 3,863 nonhydrogen protein atoms (488 amino acid residues) and 319 water oxygen atoms. The current R‐value is 20.3% for data in the resolution range of 8–2.3 Å (with 2 σ cut‐off) with good stereochemistry. The subunit structure of sweet potato β‐amylase (crystallized in the absence of α‐cyclodextrin) is very similar to that of soybean β‐amylase (complexed with α‐cyclodextrin). The root‐mean‐square (RMS) difference for 487 equivalent Cα atoms of the two β‐amylases is 0.96 Å. Each subunit of sweet potato β‐amylase is composed of a large (α/β)8 core domain, a small one made up of three long loops [L3 (residues 91–150), LA (residues 183–258), and L5 (residues 300–327)], and a long C‐terminal loop formed by residues 445–493. Conserved Glu 187, believed to play an important role in catalysis, is located at the cleft between the (α/β)8 barrel core and a small domain made up of three long loops (L3, L4, and L5). Conserved Cys 96, important in the inactivation of enzyme activity by sulfhydryl reagents, is located at the entrance of the (α/β)8 barrel. © 1995 Wiley‐Liss, Inc.
A model of the complex between interleukin‐4 and its receptors
Authors: Gustchina Alla , Zdanov Alexander , Schalk‐Hihi Céline , Wlodawer Alexander 
Published: May 2005

AbstractA three‐dimensional model of interleukin‐4 (IL‐4) bound to one molecule each of the high‐ and low‐affinity receptors (IL‐4R and IL‐2Rγ) was built, using the crystal structure of the complex of human growth hormone (HGH) with its receptor (HGHR) as a starting model. The modeling of IL‐4 with its receptors was based on the conservation of the sequences and on the predicted structural organization for cytokine receptors, and assuming that the binding mode of the ligands would be similar. Analysis of the interface between IL‐4 and both receptor molecules was carried out to reveal which residues are important for complex formation. The modeling procedures showed that there were no major problems in maintaining a reasonable fit of IL‐4 with the two receptor molecules, in a manner analogous to the complex of HGH–HGHR. Many of the residues that appear by modeling to be important for binding between IL‐4 and the receptors have been previously implicated in that role by different methods. A striking motif of aromatic and positively charged residues on the surface of the C‐terminal domains of the receptors is highly conserved in the structure of HGH–HGHR and in the models of IL‐4 complexed with its receptors. © 1995 Wiley‐Liss, Inc.
Crystallization and preliminary X‐ray diffraction studies of an a1/α2/DNA ternary complex
Authors: Li Thomas , Wolberger Cynthia , Stark Martha , Johnson Alexander D. 
Published: May 2005

AbstractCrystals have been obtained of a ternary complex containing the yeast a1/α2 homeodomain heterodimer bound to a 21‐base pair DNA site containing two 5′ overhanging bases at each end. The crystals are grown from cobaltic hexamine and form in space group P61 or P65 with a = b = 133 Å, c = 45.4 Å. Crystals that are flash‐frozen at −179°C diffract to 2.7 Å along the c‐axis and to 2.4 Å in perpendicular directions. The crystals contain one protein–DNA complex in the crystallographic asymmetric unit. © 1995 Wiley‐Liss, Inc.
Funnels, pathways, and the energy landscape of protein folding: A synthesis
Authors: Bryngelson Joseph D. , Onuchic José Nelson , Socci Nicholas D. , Wolynes Peter G. 
Published: May 2005

AbstractThe understanding, and even the description of protein folding is impeded by the complexity of the process. Much of this complexity can be described and understood by taking a statistical approach to the energetics of protein conformation, that is, to the energy landscape. The statistical energy landscape approach explains when and why unique behaviors, such as specific folding pathways, occur in some proteins and more generally explains the distinction between folding processes common to all sequences and those peculiar to individual sequences. This approach also gives new, quantitative insights into the interpretation of experiments and simulations of protein folding thermodynamics and kinetics. Specifically, the picture provides simple explanations for folding as a two‐state first‐order phase transition, for the origin of metastable collapsed unfolded states and for the curved Arrhenius plots observed in both laboratory experiments and discrete lattice simulations. The relation of these quantitative ideas to folding pathways, to uniexponential vs. multiexponential behavior in protein folding experiments and to the effect of mutations on folding is also discussed. The success of energy landscape ideas in protein structure prediction is also described. The use of the energy landscape approach for analyzing data is illustrated with a quantitative analysis of some recent simulations, and a qualitative analysis of experiments on the folding of three proteins. The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions. © 1995 Wiley‐Liss, Inc.
Modeling the quinone‐B binding site of the photosystem‐II reaction center using notions of complementarity and contact‐surface between atoms
Authors: Sobolev Vladimir , Edelman Marvin 
Published: May 2005

AbstractFunctional identity and significant similarities in cofactors and sequence exist between the L and M reaction center proteins of the photosynthetic bacteria and the D1 and D2 photosystem‐II reaction center proteins of cyanobacteria, algae, and plants. A model of the quinone (QB) binding site of the D1 protein is presented based upon the resolved structure of the QB binding pocket of the L subunit, and introducing novel quantitative notions of complementarity and contact surface between atoms. This model, built ‐without using traditional methods of molecular mechanics and restricted to residues in direct contact with QB, accounts for the experimentally derived functional state of mutants of the Dl protein in the region of QB. It predicts the binding of both the classical and phenol‐type PSII herbicides and rationalizes the relative levels of tolerance of mutant phenotypes. © 1995 Wiley‐Liss, Inc.
Dramatic differences in the motions of the mouth of open and closed cytochrome P450BM‐3 by molecular dynamics simulations
Authors: Paulsen Mark D. , Ornstein Rick L. 
Published: May 2005

AbstractMolecular dynamics trajectories were calculated separately for each of the two molecules in the asymmetric unit of the crystal structure of the hemoprotein domain of cytochrome P450BM‐3. Each simulation was 200 ps in length and included a 10 Å layer of explicit solvent. The simulated time‐average structure of each P450BM‐3 molecule is closer to its crystal structure than the two molecular dynamics time‐averaged structures are to each other. In the crystal structure, molecule 2 has a more accessible substrate binding pocket than molecule 1, and this difference is maintained throughout the simulations presented here. In particular, the substrate docking regions of molecule 1 and molecule 2 diverge in the solution state simulations. The mouth of the substrate binding pocket is significantly more mobile in the simulation of molecule 2 than in the simulation of molecule 1. For molecule 1, the width of the mouth is only slightly larger than its X‐ray value of 8.7 Å and undergoes fluctuations of about 1 Å. However, in molecule 2, the mouth of the substrate binding pocket is dramatically more open in the time‐average molecular dynamics structure (14.7 Å) than in the X‐ray structure (10.9 Å). Furthermore, this region of the protein undergoes large amplitude motions during the trajectory that are not seen in the trajectory of molecule 1, repeatedly opening and closing up to 7 Å. Presumably, the binding of different substrates will induce the mouth region to adopt different conformations from within the wide range of structures that are accessible. © 1995 Wiley‐Liss, Inc.