Evaluating molecular mechanical potentials for helical peptides and proteins
| Jazyk: | English |
|---|---|
| ISSN: | 1932-6203 |
| Přístupová URL adresa: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a0fabc1a5eeb60b86497d4e7b0cd9b9e http://europepmc.org/articles/PMC2850926?pdf=render |
| Rights: | OPEN |
| Přírůstkové číslo: | edsair.doi.dedup.....a0fabc1a5eeb60b86497d4e7b0cd9b9e |
| Autor: | Erik J. Thompson, Sarav S. Patel, Allison J. DePaul, Eric J. Sorin |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Biophysics/Theory and Simulation
Models Molecular Chemistry/Macromolecular Chemistry Insecta Magnetic Resonance Spectroscopy Biophysics/Protein Folding Computational Biology/Macromolecular Structure Analysis Beta helix lcsh:Medicine Computer Science/Applications Computational Biology/Molecular Dynamics Bioinformatics Gyration Protein Structure Secondary Force field (chemistry) Biochemistry/Protein Folding Physics/Atomic and Molecular Physics Molecular dynamics Protein structure Animals Chemistry/Biochemistry Computer Simulation lcsh:Science Polyproline helix Physics Chemistry/Physical Inorganic and Analytical Chemistry Multidisciplinary Biochemistry/Theory and Simulation lcsh:R Proteins Nuclear magnetic resonance spectroscopy Apolipoproteins Amino Acid Substitution Chemical physics Solvents Polar lcsh:Q Peptides Research Article |
| Zdroj: | PLoS ONE, Vol 5, Iss 4, p e10056 (2010) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Multiple variants of the AMBER all-atom force field were quantitatively evaluated with respect to their ability to accurately characterize helix-coil equilibria in explicit solvent simulations. Using a global distributed computing network, absolute conformational convergence was achieved for large ensembles of the capped A(21) and F(s) helical peptides. Further assessment of these AMBER variants was conducted via simulations of a flexible 164-residue five-helix-bundle protein, apolipophorin-III, on the 100 ns timescale. Of the contemporary potentials that had not been assessed previously, the AMBER-99SB force field showed significant helix-destabilizing tendencies, with beta bridge formation occurring in helical peptides, and unfolding of apolipophorin-III occurring on the tens of nanoseconds timescale. The AMBER-03 force field, while showing adequate helical propensities for both peptides and stabilizing apolipophorin-III, (i) predicts an unexpected decrease in helicity with ALA-->ARG(+) substitution, (ii) lacks experimentally observed 3(10) helical content, and (iii) deviates strongly from average apolipophorin-III NMR structural properties. As is observed for AMBER-99SB, AMBER-03 significantly overweighs the contribution of extended and polyproline backbone configurations to the conformational equilibrium. In contrast, the AMBER-99phi force field, which was previously shown to best reproduce experimental measurements of the helix-coil transition in model helical peptides, adequately stabilizes apolipophorin-III and yields both an average gyration radius and polar solvent exposed surface area that are in excellent agreement with the NMR ensemble. |
| Databáze: | OpenAIRE |
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