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Title: Do molecular dynamics force fields accurately model Ramachandran distributions of amino acid residues in water?
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 χ 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 β-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 χ 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 χ 2 values.  more » « less
Award ID(s):
1817650
NSF-PAR ID:
10335239
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Physical Chemistry Chemical Physics
Volume:
24
Issue:
5
ISSN:
1463-9076
Page Range / eLocation ID:
3259 to 3279
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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