Are Protein Force Fields Getting Better? A Systematic Benchmark on 524 Diverse NMR Measurements

被引:306
作者
Beauchamp, Kyle A. [1 ]
Lin, Yu-Shan [2 ]
Das, Rhiju [1 ,3 ]
Pande, Vijay S. [1 ,2 ]
机构
[1] Stanford Univ, Biophys Program, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Chem, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA
关键词
WATER MODEL; SIMULATIONS; BACKBONE; DYNAMICS; HELIX; UBIQUITIN; PEPTIDE; REPARAMETRIZATION; ENERGETICS; MECHANICS;
D O I
10.1021/ct2007814
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Recent hardware and software advances have enabled simulation studies of protein systems on biophysically relevant time scales, often revealing the need for improved force fields. Although early force field development was limited by the lack of direct comparisons between simulation and experiment, recent work from several laboratories has demonstrated direct calculation of NMR observables from protein simulations. Here, we quantitatively evaluate 11 recent molecular dynamics force fields in combination with 5 solvent models against a suite of 524 chemical shift and J coupling ((3)JH(N)H(omega) (3)JH(N)C(beta), (3)JH(alpha)C', (3)JH(N)C', and (3)JH(alpha)N) measurements on dipeptides, tripeptides, tetra-alanine, and ubiquitin. Of the force fields examined (ff96, ff99, ff03, ff03*, ff03w, ff99sb*, ff99sb-ildn, ff99sb-ildn-phi, ff99sb-ildn-NMR, CHARMM27, and OPLS-AA), two force fields (ff99sb-ildn-phi, ff99sb-ildn-NMR) combining recent side chain and backbone torsion modifications achieved high accuracy in our benchmark. For the two optimal force fields, the calculation error is comparable to the uncertainty in the experimental comparison. This observation suggests that extracting additional force field improvements from NMR data may require increased accuracy in J coupling and chemical shift prediction. To further investigate the limitations of current force fields, we also consider conformational populations of dipeptides, which were recently estimated using vibrational spectroscopy.
引用
收藏
页码:1409 / 1414
页数:6
相关论文
共 47 条
[31]   Optimizing Protein-Solvent Force Fields to Reproduce Intrinsic Conformational Preferences of Model Peptides [J].
Nerenberg, Paul S. ;
Head-Gordon, Teresa .
JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2011, 7 (04) :1220-1230
[32]   Exploring protein native states and large-scale conformational changes with a modified generalized born model [J].
Onufriev, A ;
Bashford, D ;
Case, DA .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2004, 55 (02) :383-394
[33]   POLYMORPHIC TRANSITIONS IN SINGLE-CRYSTALS - A NEW MOLECULAR-DYNAMICS METHOD [J].
PARRINELLO, M ;
RAHMAN, A .
JOURNAL OF APPLIED PHYSICS, 1981, 52 (12) :7182-7190
[34]   How Robust Are Protein Folding Simulations with Respect to Force Field Parameterization? [J].
Piana, Stefano ;
Lindorff-Larsen, Kresten ;
Shaw, David E. .
BIOPHYSICAL JOURNAL, 2011, 100 (09) :L47-L49
[35]   Self-consistent 3J coupling analysis for the joint calibration of Karplus coefficients and evaluation of torsion angles [J].
Schmidt, JM ;
Blümel, M ;
Löhr, F ;
Rüterjans, H .
JOURNAL OF BIOMOLECULAR NMR, 1999, 14 (01) :1-12
[36]   A NEUTRAL, WATER-SOLUBLE, ALPHA-HELICAL PEPTIDE - THE EFFECT OF IONIC-STRENGTH ON THE HELIX COIL EQUILIBRIUM [J].
SCHOLTZ, JM ;
YORK, EJ ;
STEWART, JM ;
BALDWIN, RL .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (13) :5102-5104
[37]   DISTRIBUTION OF HELICITY WITHIN THE MODEL PEPTIDE ACETYL(AAQAA)(3)AMIDE [J].
SHALONGO, W ;
DUGAD, L ;
STELLWAGEN, E .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (18) :8288-8293
[38]   Anton, a special-purpose machine for molecular dynamics simulation [J].
Shaw, David E. ;
Deneroff, Martin M. ;
Dror, Ron O. ;
Kuskin, Jeffrey S. ;
Larson, Richard H. ;
Salmon, John K. ;
Young, Cliff ;
Batson, Brannon ;
Bowers, Kevin J. ;
Chao, Jack C. ;
Eastwood, Michael P. ;
Gagliardo, Joseph ;
Grossman, J. P. ;
Ho, C. Richard ;
Ierardi, Douglas J. ;
Kolossvary, Istvan ;
Klepeis, John L. ;
Layman, Timothy ;
Mcleavey, Christine ;
Moraes, Mark A. ;
Mueller, Rolf ;
Priest, Edward C. ;
Shan, Yibing ;
Spengler, Jochen ;
Theobald, Michael ;
Towles, Brian ;
Wang, Stanley C. .
COMMUNICATIONS OF THE ACM, 2008, 51 (07) :91-97
[39]   Atomic-Level Characterization of the Structural Dynamics of Proteins [J].
Shaw, David E. ;
Maragakis, Paul ;
Lindorff-Larsen, Kresten ;
Piana, Stefano ;
Dror, Ron O. ;
Eastwood, Michael P. ;
Bank, Joseph A. ;
Jumper, John M. ;
Salmon, John K. ;
Shan, Yibing ;
Wriggers, Willy .
SCIENCE, 2010, 330 (6002) :341-346
[40]   SPARTA plus : a modest improvement in empirical NMR chemical shift prediction by means of an artificial neural network [J].
Shen, Yang ;
Bax, Ad .
JOURNAL OF BIOMOLECULAR NMR, 2010, 48 (01) :13-22