krapnik's conformational [at least 200 articles]

Abstract

Conformational energy calculations using ECEPP (Empirical Conformational Energy Program for Peptides) were performed on the molecular fragment Calpha1C'ONHCalpha2, on N-methylacetamide, and on several peptide molecules including N-acetyl-N'-methylglycineamide (Gly single residue), N-acetyl-N',N'-dimethylglycine-amide, and N-acetyl-N'-methylamide dipeptides of Gly-Gly and Gly-Pro. Energy minimization was carried out with peptide groups taken in both the cis and trans conformations, and the librational entropy and conformational free energy were determined at each minimum. It was found that the instability of cis in Gly-Gly comes primarily from interactions ...

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Cited By: 20, Export Date: 19 January 06, Source: Scopus

Abstract

High-sensitivity differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy were used to study the interaction of a synthetic alpha -helical hydrophobic transmembrane peptide, acetyl-Lys(2)-(Leu-ala)(12)-Lys(2)-amide [(LA)(12)], and members of a homologous series of n-saturated diacylphosphatidylethanolamines (PEs). Ln the lower range of peptide mole fractions, the DSC endotherms exhibited by the lipid/peptide mixtures consist of two components. The temperature and cooperativity of the sharper, higher temperature component are very similar to those of pure PE bilayers and are almost unaffected by ...

Abstract

The role of side-chain entropy (SCE) in protein folding has long been speculated about but is still not fully understood. Utilizing a newly developed Monte Carlo method, we conducted a systematic investigation of how the SCE relates to the size of the protein and how it differs among a protein's X-ray, NMR, and decoy structures. We estimated the SCE for a set of 675 nonhomologous proteins, and observed that there is a significant SCE for both exposed and buried residues for ...

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Cited By (since 1996): 1Export Date: 7 September 2007Source: Scopus

Abstract

By employing thousands of PCs and new worldwide-distributed computing techniques, we have simulated in atomistic detail the folding of a fast-folding 36-residue alpha-helical protein from the villin headpiece. The total simulated time exceeds 300 mus, orders of magnitude more than previous simulations of a molecule of this size. Starting from an extended state, we obtained an ensemble of folded structures, which is on average 1.7 Angstrom and 1.9 Angstrom away from the native state in C-alpha distance-based root-mean-square deviation (dRMS) and ...

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Times Cited: 59

Abstract

We report a blind test of lattice-model-based search strategies for finding global minima of model protein chains. One of us (E.I.S.) selected 10 compact conformations of 48-mer chains on the three-dimensional cubic lattice and used their inverse folding algorithm to design HP (H, hydrophobic; P, polar) sequences that should fold to those ”target” structures. The sequences, but not the structures, were sent to the UCSF group (K.Y., K.M.F., P.D.T., H.S.C., and K.A.D.), who used two methods to attempt to find the ...

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Times Cited: 137ArticleEnglishYUE, KUNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,BOX 1204,SAN FRANCISCO,CA 94143Cited References Count: 33QB238NATL ACAD SCIENCES2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418WASHINGTON

Abstract

A challenge in computational protein folding is to assemble secondary structure elements-helices and strands-into well-packed tertiary structures. Particularly difficult is the formation of beta -sheets from strands, because they involve large conformational searches at the same time as precise packing and hydrogen bonding. Here we describe a method, called Geocore-2, that (I) grows chains one monomer or secondary structure at a time, then (2) disconnects the loops and performs a fast rigid-body ducking step to achieve canonical packings, then (3) in ...

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Times Cited: 17ArticleEnglishDill, K. AUniv Calif San Francisco, Dept Pharmaceut Chem, Box 1204, San Francisco, CA 94143 USACited References Count: 34374DHCAMBRIDGE UNIV PRESS40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USANEW YORK

Abstract

We describe a computer algorithm for predicting the three-dimensional structures of proteins using only their amino acid sequences. The method differs from others in two ways: (I)it uses very few energy parameters, representing hydrophobic and polar interactions, and (2) it uses a new ”constraint-based exhaustive” searching method, which appears to be among the fastest and most complete search methods yet available for realistic protein models. It finds a relatively small number of low-energy conformations, among which are native-like conformations, for crambin ...

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Times Cited: 65ArticleEnglishCited References Count: 36TU724CAMBRIDGE UNIV PRESS40 WEST 20TH STREET, NEW YORK, NY 10011-4211NEW YORK

Abstract

We model proteins as copolymer chains of H (hydrophobic) and P (polar) monomers configured as self-avoiding flights on three-dimensional simple-cubic lattices. The HH interaction is favorable. The folding problem is to find the ”native” conformation(s) (lowest free energy) for an HP sequence. Using geometric proofs for self-avoiding lattice chains, we develop equations relating a monomer sequence to its native structures. These constraint relations can be used for two purposes: (1) to compute a tight lower bound on the free energy of ...

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Times Cited: 50ArticleEnglishYUE, K. ZUNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,BOX 1204,SAN FRANCISCO,CA 94143Cited References Count: 25LY667AMERICAN PHYSICAL SOCONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USACOLLEGE PK

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Times Cited: 40ArticleEnglishHighsmith, SUniv Pacific, Sch Dent, Dept Biochem, 2155 Webster St, San Francisco, CA 94115 USACited References Count: 53233JRCAMBRIDGE UNIV PRESS40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USANEW YORK

Abstract

A few years ago, lattice model studies indicated that compactness could induce polymer chains to develop protein-like secondary structures. Subsequent off-lattice studies have found the amounts of induced structure to be relatively small. Here we use distance geometry to generate random conformations of compact poly-alanine chains of various chain lengths. The poly-alanine chains are subjected only to compactness and excluded volume constraints; no other energies or conformational propensities are included in the chain generation procedure. We find that compactness leads to ...

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Times Cited: 55ArticleEnglishYEE, D. PUNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143Cited References Count: 34PD619ACADEMIC PRESS LTD24-28 OVAL RD, LONDON, ENGLAND NW1 7DXLONDON

Abstract

The sources of the stability of a type VI turn formed with high population in the cis isomeric form of an unblocked six residue peptide, Ser(1)-Tyr(2)-Pro(3)-Tyr(4)-Asp(5)-Val(6) (SYPYDV), were investigated by making extensive amino acid substitutions at residues 2, 4 and 5. Several NMR parameters indicate the presence of the turn, including significant upheld shifts of the proton resonances of the cis proline, a small (3)J(HN alpha) coupling constant for residue 2, a cross-turn d(alpha N)(i,i + 2) NOE from residue 2 ...

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Times Cited: 133ArticleEnglishCited References Count: 37PQ663ACADEMIC PRESS LTD24-28 OVAL RD, LONDON, ENGLAND NW1 7DXLONDON

Abstract

The intrinsic chemical shift dispersion for N-15, (HN)-H-1, C-13(alpha), H-1(alpha), C-13(beta) and (CO)-C-13 resonances has been evaluated utilizing complete resonance assignment data for unfolded apomyoglobin, together with two other unfolded and five folded proteins, obtained from the literature. The dispersion of C-13(alpha), H-1(alpha), and C-13(beta) resonances for the unfolded proteins is poor, whereas the dispersion of N-15, (HN)-H-1 and (CO)-C-13 is much greater, reflecting the sensitivity of these nuclei to the nature of the neighboring amino acid in the primary sequence, ...

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Times Cited: 58ArticleEnglishDyson, H. JSalk Inst Biol Studies, Dept Mol Biol, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USACited References Count: 31YM709ELSEVIER SCIENCE BVPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSAMSTERDAM

Abstract

Structures have been calculated for the folded conformation found at high population in the cis isomeric form of the peptide NH3+-Ser-Tyr-Pro-Phe-Asp-Val-COO- (SYPFDV) in aqueous solution, using distance geometry and restrained molecular dynamics. A number of NMR parameters, including NOE distance restraints and phi and chi(1) dihedral angle restraints derived from coupling constants were used in the calculation. The restraints were carefully selected to exclude those that might ha ire a significant contribution from the unfolded states of the peptide, so that ...

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Times Cited: 96ArticleEnglishCited References Count: 32PQ663ACADEMIC PRESS LTD24-28 OVAL RD, LONDON, ENGLAND NW1 7DXLONDON

Abstract

Apomyoglobin forms a denatured state under low-salt conditions at pH 2.3. The conformational propensities and polypeptide backbone dynamics of this state have been characterized by NMR. Nearly complete backbone and some side chain resonance assignments have been obtained, using a triple-resonance assignment strategy tailored to low protein concentration (0.2 mM) and poor chemical shift dispersion. An estimate of the population and location of residual secondary structure has been made by examining deviations of C-13(alpha), (CO)-C-13, and H-1(alpha) chemical shifts from random ...

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Times Cited: 119ArticleEnglishWright, P. EScripps Res Inst, Dept Mol Biol MB2, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USACited References Count: 59416UJAMER CHEMICAL SOC1155 16TH ST, NW, WASHINGTON, DC 20036 USAWASHINGTON

Abstract

The factors that determine the stability of antiparallel beta-she ets are considered via a theoretical analysis of conformational free energies. A series of idealized model polyalanine beta-sheets are built with constraints such that the angular geometry of hydrogen bonding varies in the range observed in proteins while hydrogen bonding distance remains fixed. The conformations of the sheets generated in this way have a broad distribution of twist angles ranging from highly twisted left-handed to highly twisted right-handed orientations. The association free ...

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Times Cited: 111ArticleEnglishCited References Count: 30RV944ACADEMIC PRESS (LONDON) LTD24-28 OVAL RD, LONDON, ENGLAND NW1 7DXLONDON

Abstract

The Zimm-Bragg parameters s and sigma are calculated for the helix-coil transition of poly-L-alanine. The theoretical approach involves evaluating gas phase conformational energies for both coil and helical states using the CHARMM potential function and accounting for solvation effects with various continuum solvation models. Conformational free energies are then incorporated into a formalism developed by Go et al. for the calculation of s and sigma. Calculated values for both sand sigma as well as the enthalpy change associated with helix formation ...

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Times Cited: 165ArticleEnglishCited References Count: 66RV944ACADEMIC PRESS (LONDON) LTD24-28 OVAL RD, LONDON, ENGLAND NW1 7DXLONDON

Abstract

The stability of beta-turns is calculated as a function of sequence and turn type with a Monte Carlo sampling technique. The conformational energy of four internal hydrogen-bonded turn types, I, I', II and II', is obtained by evaluating their gas phase energy with the CHARMM force field and accounting for solvation effects with the Finite Difference Poisson-Boltzmann (FDPB) method. All four turn types are found to be less stable than the coil state, independent of the sequence in the turn. The ...

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Times Cited: 76ArticleEnglishCited References Count: 51UT105ACADEMIC PRESS LTD24-28 OVAL RD, LONDON, ENGLAND NW1 7DXLONDON

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Wu2004A recently proposed dynamical method [A. Laio and M. Parrinello, Proc. Natl. Acad. Sci. U.S.A. 99, 12562 (2002)] allows us to globally sample the free energy surface. This approach uses a coarse-grained non-Markovian dynamics to bias microscopic atomic trajectories. After a sufficiently long simulation time, the global free energy surface can be reconstructed from the non-Markovian dynamics. Here we apply this scheme to study the T=0 free energy surface, i.e., the potential energy surface in coarse-grained space. We show that the

Abstract

We present a method for the computer-based iterative assembly of native-like tertiary structures of helical proteins from cx-helical fragments. Forany pair of helices, our method, called MATCHSTIX, first generates an ensemble of possible relative orientations of the helices with various ways to form hydrophobic contacts between them. Those conformations having steric clashes, or a large radius of gyration of hydrophobic residues, or with helices too far separated to be connected by the intervening linking region, are discarded. Then, we attempt to ...

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Times Cited: 0ArticleEnglishDill, K. AUniv Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USACited References Count: 46337JACELL PRESS600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USACAMBRIDGE

Abstract

Many cellular proteins are intrinsically disordered and undergo folding, in whole or in part, upon binding to their physiological targets. The past few years have seen an exponential increase in papers describing characterization of intrinsically disordered proteins, both free and bound to targets. Although NMR spectroscopy remains the favored tool, a number of new biophysical techniques are proving exceptionally useful in defining the limits of the conformational ensembles. Advances have been made in prediction of the recognition elements in disordered proteins, ...

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Times Cited: 0ArticleEnglishWright, P. EScripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USACited References Count: 65420IHCURRENT BIOLOGY LTD84 THEOBALDS RD, LONDON WC1X 8RR, ENGLANDLONDON

Abstract

A major challenge in the post-genome era will be determination of the functions of the encoded protein sequences. Since it is generally assumed that the function of a protein is closely linked to its three-dimensional structure, prediction or experimental determination of the library of protein structures is a matter of :high priority. However, a large proportion of gene sequences appear to;code not for folded, globular proteins, but for long stretches of amino acids that are likely to be either unfolded in ...

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JWright, PE, Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USAOCT 22 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA.

Abstract

The dynamic behavior of the ribonuclease inhibitor barstar has been investigated by molecular dynamics (MD) simulations in explicit water. Two 2.5 ns MD simulations were performed, and an ensemble of 25 000 structures was generated. This ensemble reproduces the solution structures and is consistent with the experimental structural restraints from NMR spectroscopy. Reorientation of the backbone NH bond vectors and side chain methyl groups was monitored by calculation of autocorrelation functions and the generalized S-2 Order parameters. Order parameters derived for ...

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Times Cited: 28

Abstract

The detailed characterization of denatured proteins remains elusive due to their mobility and conformational heterogeneity. NMR studies are beginning to provide clues regarding residual structure in the denatured state but the resulting data are too sparse to be transformed into molecular models using conventional techniques. Molecular dynamics simulations can complement NMR by providing detailed structural information for components of the denatured ensemble. Here, we describe three independent 4 ns high-temperature molecular dynamics simulations of barnase in water. The simulated denatured state ...

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Times Cited: 85

Abstract

Extensive measurements and analysis of thermodynamic stability and kinetics of urea-induced unfolding and folding of hisactophilin are reported for 5-50 degreesC, at pH 6.7. Under these conditions hisactophilin has moderate thcrmodynamic stability, and equilibrium and kinetic data are well fit by a two-state transition between the native and the denatured states. Equilibrium and kinetic m values decrease with increasing temperature, and decrease with increasing denaturant concentration. The OF values at different temperatures and urea concentrations are quite constant, however, at about ...

Abstract

Background: Rop is an RNA binding, dimeric, four-helix bundle protein with a well-defined, regular hydrophobic core ideally suited for redesign studies. A family of Rop variants in which the hydrophobic core was systematically redesigned has previously been created and characterized. Results: We present a structural and thermodynamic analysis of Ala(2)lle(2)-6, a variant of Rop with an extensively redesigned hydrophobic core. The structure of Ala(2)lle(2)-6 reveals a completely new fold formed by a conformational "flip" of the two protomers around the dimeric ...

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Wang2000In this study, we present conformational energies for a molecular mechanical model (Parm99) developed for organic and biological molecules using the restrained electrostatic potential (RESP) approach to derive the partial charges. This approach uses the simple ldquogenericrdquo force field model (Parm94), and attempts to add a minimal number of extra Fourier components to the torsional energies, but doing so only when there is a physical justification. The results are quite encouraging, not only for the 34-molecule set that has been studied

Abstract

Myoglobin has been extensively studied as a model system for protein folding in vitro. As part of an ongoing study of myoglobin folding, we have synthesized a series of peptide fragments corresponding to portions of the sequence of the sperm whale protein. The conformational preferences of these peptides have been investigated by circular dichroism and nuclear magnetic resonance spectroscopy in aqueous solution. In this paper we describe the folding propensities of two peptides (Mb-G and Mb-H), corresponding to the G- and ...

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Times Cited: 190ArticleEnglishCited References Count: 71LN618AMER CHEMICAL SOC1155 16TH ST, NW, WASHINGTON, DC 20036WASHINGTON

Abstract

The side chains of Arg 31, Glu 36 and Arc 40 in Are repressor form a buried salt-bridge triad. The entire salt-bridge network can be replaced by hydrophobic residues in combinatorial randomization experiments resulting in active mutants that are significantly more stable than wild type. The crystal structure of one mutant reveals that the mutant side chains pack against each ether in an otherwise wild-type fold. Thus, simple hydrophobic interactions provide more stabilizing energy than the buried salt bridge and confer ...

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Rf665Times Cited:225Cited References Count:28

Abstract

The helix-coil transition of poly(L-lysine) in water and in methanol solutions of a 1:1 salt is studied as a function of pH. The relative electrostatic free energy between the ionized microstates of poly(L-lysine) is evaluated as the sum of the potentials of mean force (PMF) between pairs of charged lysine residues. The PMFs in the alpha-helical and the statistical-coil conformations in water and in methanol-water solutions were calculated with a continuum electrostatic model based on a numerical solution of the nonlinear ...

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Times Cited: 22ArticleEnglishVOROBJEV, Y. NCORNELL UNIV,BAKER LAB CHEM,ITHACA,NY 14853Cited References Count: 39QW705AMER CHEMICAL SOCPO BOX 57136, WASHINGTON, DC 20037-0136WASHINGTON

Abstract

It has long been proposed that much of the information encoding how a protein folds is contained locally in the peptide chain. Here we present a large-scale simulation study designed to examine the extent to which conformations of peptide fragments in water predict native conformations in proteins. We perform replica exchange molecular dynamics (REMD) simulations of 872 8-mer, 12-mer, and 16-mer peptide fragments from 13 proteins using the AMBER 96 force field and the OBC implicit solvent model. To analyze the ...

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Times Cited: 0ArticleEnglishVoelz, V. AStanford Univ, Dept Chem, Stanford, CA 94305 USACited References Count: 34415HIPUBLIC LIBRARY SCIENCE185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USASAN FRANCISCO

Abstract

It has been proposed that proteins fold by a process called "Zipping and Assembly" (Z&A). Zipping refers to the growth of local substructures within the chain, and assembly refers to the coming together of already-formed pieces. Our interest here is in whether Z&A is a general method that can fold most of sequence space, to global minima, efficiently. Using the HP model, we can address this question by enumerating full conformation and sequence spaces. We find that Z&A reaches the global ...

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Times Cited: 10ArticleEnglishDill, K. AUniv Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USACited References Count: 33137MGWILEY-LISSDIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USAHOBOKEN

Abstract

A template-assisted conformational change of the cellular prion protein (PrPC) from a predominantly helical structure to an amyloid-type structure with a higher proportion of beta -sheet is thought to be the causative factor in prion diseases. Since flexibility of the polypeptide is likely to contribute to the ability of PrPC to undergo the conformational change that leads to the infective state, we have undertaken a comprehensive examination of the dynamics of two recombinant Syrian hamster PrP fragments, PrP(29-231) and PrP(90-231), using ...

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Times Cited: 79ArticleEnglishDyson, H. JScripps Res Inst, Dept Mol Biol, MB-2,10550 N Torrey Pines Rd, La Jolla, CA 92037 USACited References Count: 57407FLAMER CHEMICAL SOC1155 16TH ST, NW, WASHINGTON, DC 20036 USAWASHINGTON

Abstract

Glycodendrimers bearing Tn (alpha-D-Ga1NAc-(1-->O)-Ser/Thr), an identified tumor-associated carbohydrate antigen, hold promise in the post-surgery treatment of a variety of tumors such as metastatic breast cancer. We used molecular dynamics (MD) techniques to examine structural differences taking place during synthesis of two classes of tetravalent Multiple Antigen Glycopeptides (MAG) that differ only by the gamma-Abu insert in the structure of the oligolysine core. Each of the selected intermediates of the synthesis was modeled, subjected to the 2 ns run in N,N'-dimethylformamide (DMF) ...

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840NITimes Cited:2Cited References Count:42

Abstract

We have designed de novo 13 divergent spectrin SH3 core sequences to determine their folding properties. Kinetic analysis of the variants with stability similar to that of the wild type protein shows accelerated unfolding and refolding rates compatible with a preferential stabilization of the transition state. This is most likely caused by conformational strain in the native state, as deletion of a methyl group (Ile-->Val) leads to deceleration in unfolding and increased stability (up to 2 kcal x mol(-1)). Several of ...

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1072-8368Journal Article

Abstract

Globular proteins are characterized by the specific and tight packing of hydrophobic side-chains in the so-called "hydrophobic core." Formation of the core is key in folding, stabilization, and conformational specificity. The critical role of hydrophobic cores in maintaining the highly ordered structures present in natural proteins justifies the tremendous efforts devoted to their redesign. Both experimental and computational combinatorial-based approaches have been reported in the last years as powerful protein design tools. These manage to explore large regions of the sequence/conformational ...

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1097-0134Journal ArticleReviewReview, Tutorial

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Times Cited: 1CorrectionEnglishCited References Count: 1916ZNAMER CHEMICAL SOC1155 16TH ST, NW, WASHINGTON, DC 20036 USAWASHINGTON

Abstract

Escherichia coli dihydrofolate reductase (DHFR) has several flexible loops surrounding the active site that play a functional role in substrate and cofactor binding and in catalysis. We have used heteronuclear NMR methods to probe the loop conformations in solution in complexes of DHFR formed during the catalytic cycle. To facilitate the NMR analysis, the enzyme was labeled selectively with [N-15]-alanine. The 13 alanine resonances provide a fingerprint of the protein structure and report on the active site loop conformations and binding ...

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Times Cited: 29ArticleEnglishWright, P. EScripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USACited References Count: 27882KLAMER CHEMICAL SOC1155 16TH ST, NW, WASHINGTON, DC 20036 USAWASHINGTON

Abstract

Empirical potential energy calculations have been carried out to determine the preferred conformations of penicillins and penicillin sulphones and their 1-oxa-1-dethia and 1-carba-1-dethia analogues. With the exception of 1-oxa-1-dethia penicillins, all the other compounds favour C2 and the C3 puckered conformations of their five-membered rings. Replacement of C2 methyl groups by hydrogen atoms as in bisnorpenicillin V or oxidation of sulphur in position l as in sulphones, makes the C3 puckered form much less favourable. Addition of an amino-acyl group at ...

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Cited By: 0, Export Date: 19 January 06, Source: Scopus

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Vaart2006Abstract Conformational transitions are essential for the functioning of many proteins, and understanding this dynamical behavior is a central goal in molecular biology. Computer simulations are playing an important role towards this aim by providing insights into how the conformational changes are induced, propagated and used. Popular methods for the simulation of conformational transitions will be reviewed, with a focus on atomistic molecular dynamics techniques for the calculation of transition pathways article

Abstract

The earliest steps in the folding of proteins are complete on an extremely rapid time scale that is difficult to access experimentally. We have used rapid-mixing quench-flow methods to extend the time resolution of folding studies on apomyoglobin and elucidate the structural and dynamic features of members of the ensemble of intermediate states that are populated on a submillisecond time scale during this process. The picture that emerges is of a continuum of rapidly interconverting states. Even after only 0.4 ms ...

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Times Cited: 0ArticleEnglishTakahashi, SKyoto Univ, Grad Sch Engn, Kyoto 6158510, JapanCited References Count: 39351QGNATL ACAD SCIENCES2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USAWASHINGTON

Abstract

We perform all-atom computer simulations on nearly one hundred 6-, 8-, 10-, and 12-mer peptide fragments of protein G, and look for stable states. We simulated by replica-exchange molecular dynamics using Amber7 with the parm96 force-field and a GB/SA (generalized-Born/solvent accessible) implicit solvent model. We find that useful diagnostics for identifying stable converged structures are the conformational entropy and free energy of each state. A large gap in the ground-state free-energy, and a low entropy indicate convergence to a single preferred ...

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Times Cited: 0ArticleEnglishUrbic, TUniv Ljubljana, Fac Chem & Chem Technol, Ljubljana 61000, SloveniaCited References Count: 46326AOSLOVENSKO KEMIJSKO DRUSTVOHAJDRIHOVA 19, LJUBLJANA 1000, SLOVENIALJUBLJANA

Abstract

The DNA binding domain of c-Myb, protein, a regulator of the transcription, consists of three homologous tandem repeats (R1, R2 and R3) with 51-52 amino acid residues. Previously, we found that the thermal transition of the binding domain (R1R2R3) is three-state transition and that the intermediate state is related to the lower stability of R2 than the other two. In order to clarify the thermodynamic characteristics of the most unstable R2, we synthesized two mutants of R2, R2(V103I) and R2(V103L), and ...

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Times Cited: 2ArticleEnglishTULLIS, R. HCALIF BIOMED RES FDN,LA JOLLA,CA 92121Cited References Count: 22LS978AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC9650 ROCKVILLE PIKE, BETHESDA, MD 20814BETHESDA

Abstract

Traditionally, molecular disorder has been viewed as local or global instability. Molecules or regions displaying disorder have been considered inherently unstructured. The term has been routinely applied to cases for which no atomic coordinates can be derived from crystallized molecules. Yet, even when it appears that the molecules are disordered, prevailing conformations exist, with population times higher than those of all alternate conformations. Disordered molecules are the outcome of rugged energy landscapes away from the native state around the bottom of ...

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Times Cited: 16ReviewEnglishCited References Count: 52463llAlternate Journal: ProteinsProteinsLabel: Wiley-Liss

Abstract

Here we review different aspects of the protein folding literature. We present a broad range of observations, showing them to be consistent with a general hierarchical protein folding model. In such a model, local relatively stable, conformationally fluctuating building blocks bind through population selection, to yield the native state. The model includes several components: (1) the fluctuating building blocks that constitute local minima along the polypeptide chain, which even if unstable still possess higher population times than all alternate conformations; (2) ...

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Times Cited: 15ReviewEnglishCited References Count: 122490bjAlternate Journal: Crit Rev Biochem MolCrit Rev Biochem MolLabel: Crc Press Llc

Abstract

Folding funnels have been the focus of considerable attention during the last few years. These have mostly been discussed in the general context of the theory of protein folding. Here we extend the utility of the concept of folding funnels, relating them to biological mechanisms and function. In particular, here we describe the shape of the funnels in light of protein synthesis and folding; flexibility, conformational diversity, and binding mechanisms; and the associated binding funnels, illustrating the multiple routes and the ...

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Times Cited: 99ReviewEnglishCited References Count: 66203keAlternate Journal: Protein SciProtein SciLabel: Cambridge Univ Press

Abstract

The cis/trans conformational equilibrium of N-methyl formamide (NMF) and the sterically hindered tert-butylformamide (TBF) was investigated by the use of variable temperature gradient H-1 NMR in aqueous solution and in the low dielectric constant and solvation ability solvent CDCl3 and various levels of first principles calculations. The trans isomer of NMF in aqueous solution is enthalpically favored relative to the cis (Delta H degrees = -5.79 +/- 0.18 kJ mol(-1)) with entropy differences at 298 K (298 center dot AS degrees ...

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JABLSTROM P, 1988, J AM CHEM SOC, V110, P4198; AUBRY A, 1981, INT J PEPT PROT RES, V18, P195; AUBRY A, 1985, J AM CHEM SOC, V107, P7640; BARONE V, 1997, J CHEM PHYS, V107, P3210; BARONE V, 1998, J COMPUT CHEM, V19, P404; BARONE V, 1998, J PHYS CHEM A, V102, P1995; BECKE AD, 1993, J CHEM PHYS, V98, P5648; BERENDSEN HJC, 1986, ANN NY ACAD SCI, V482, P269; BOUSSARD G, 1985, J AM CHEM SOC, V107, P1825; BROWN RD,

Abstract

The gas-phase structures of N,N-dimethylvinylamine, (CH3)(2)NC(H)=CH2 (1), and perfluoro-N,N-dimethylvinylamine, (CF3)(2)NC(F)=CF2 (2), were determined by gas electron diffraction and quantum chemical methods (B3LYP and MP2 with 6-31G* basis sets). The configuration around nitrogen is slightly pyramidal in both compounds, with the sum of the nitrogen bond angles 351.2(12)degrees and 354 8(6)degrees in 1 and 2, respectively. In the parent compound 1, the (CH3)(2)N group lies nearly in the plane of the vinyl group, and the nitrogen lone pair (lp) is almost perpendicular ...

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JABE T, 1989, CHEM LETT, P905; BROWN RD, 1987, J MOL SPECTROSC, V124, P34; CAHILL P, 1968, J CHEM PHYS, V48, P1620; CHANG PLF, 1969, J ORG CHEM, V34, P2791; CURL RF, 1959, J CHEM PHYS, V30, P1529; FRISCH MJ, 1998, GAUSSIAN98 VERSION A; GLENDENING ED, 1990, NBO VERSION 3 1; HAFELINGER G, 1994, CHEM ENAMINES, P1; HEDBERG L, 1993, J MOL SPECTROSC, V160, P117; LEIBOLD C, 1997, J ORG CHEM, V62, P6160; LOVAS FJ, 1975, J CHEM PHYS, V62, P1925;

Abstract

Weakly polar interactions between the side-chain aromatic rings and hydrogens of backbone amides (Ar-HN) are found in unique conformational regions. To characterize these conformational regions and to elucidate factors that determine the conformation of the Ar-HN interactions, four 4-ns molecular dynamics simulations were performed using four different low-energy conformations obtained from simulated annealing and one extended conformation of the model tripeptide Ac-Phe-Gly-Gly-NH-CH3 as starting structures. The Ar(i)-HN(i+1) interactions were 4 times more frequent than were Ar(i)-HN(i+2) interactions. Half of the conformations ...

Note (first note only)

JLovas, S, Creighton Univ, Sch Med, Dept Biomed Sci, 2500 Calif Plaza, Omaha, NE 68178 USANOV 28 Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA.

Abstract

The active site of aspartic proteases is covered by one or more flaps, which control access to the active site and play a significant role in the binding of the substrate. An extensive conformational change of the flaps takes place upon binding of substrate to the active site. A long molecular dynamics simulation was performed on the complex consisting of a peptide (CA-p2) from a natural substrate cleavage site of the gag/pol polyprotein placed in the active site of HIV-1 protease ...

Note (first note only)

JMAY 30