Journal article
Do molecular dynamics force fields accurately model Ramachandran distributions of amino acid residues in water?
Physical chemistry chemical physics : PCCP, Vol.24(5), pp.3259-3279
06 Jan 2022
PMID: 35048087
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Molecular dynamics (MD) is a powerful tool for studying intrinsically disordered proteins, however, its reliability depends on the accuracy of the force field. We assess Amber ff19SB, Amber ff14SB, OPLS-AA/M, and CHARMM36m with respect to their capacity to capture intrinsic conformational dynamics of 14 guest residues x (=G, A, L, V, I, F, Y, D-P, E-P, R, C, N, S, T) in GxG peptides in water. The MD-derived Ramachandran distribution of each guest residue is used to calculate 5 J-coupling constants and amide I ' band profiles to facilitate a comparison to spectroscopic data through reduced chi(2) functions. We show that the Gaussian model, optimized to best fit the experimental data, outperforms all MD force fields by an order of magnitude. The weaknesses of the MD force fields are: (i) insufficient variability of the polyproline II (pPII) population among the guest residues; (ii) oversampling of antiparallel at the expense of transitional beta-strand region; (iii) inadequate sampling of turn-forming conformations for ionizable and polar residues; and (iv) insufficient guest residue-specificity of the Ramachandran distributions. Whereas Amber ff19SB performs worse than the other three force fields with respect to chi(2) values, it accounts for residue-specific pPII content better than the other three force fields. Additional testing of residue-specific RSFF1 and Amber ff14SB combined with TIP4P/2005 on six guest residues x (=A, I, F, D-P, R, S) reveals that residue specificity derived from protein coil libraries or an improved water model alone do not result in significantly lower chi(2) values.
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Details
- Title
- Do molecular dynamics force fields accurately model Ramachandran distributions of amino acid residues in water?
- Creators
- Brian Andrews - Drexel Univ, Dept Phys, Philadelphia, PA 19104 USAJose Guerra - SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USAReinhard Schweitzer-Stenner - Drexel UniversityBrigita Urbanc - Drexel University
- Publication Details
- Physical chemistry chemical physics : PCCP, Vol.24(5), pp.3259-3279
- Publisher
- Royal Soc Chemistry
- Number of pages
- 21
- Grant note
- Drexel's University Research Computing Facility MCB-1817650; OAC-1919691 / National Science Foundation; National Science Foundation (NSF)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Identifiers
- 991019168085504721
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- Domestic collaboration
- Web of Science research areas
- Chemistry, Physical
- Physics, Atomic, Molecular & Chemical