Quantifying uncertainty and sampling quality in biomolecular simulations.
Growing computing capacity and algorithmic advances have facilitated the study of increasingly large biomolecular systems at longer timescales. However, with these larger, more complex systems come questions about the quality of sampling and statistical convergence. What size systems can be sampled fully? If a system is not fully sampled, can certain "fast variables" be considered well-converged? How can one determine the statistical significance of observed results? The present review describes statistical tools and the underlying physical ideas necessary to address these questions. Basic definitions and ready-to-use analyses are provided, along with explicit recommendations. Such statistical analyses are of paramount importance in establishing the reliability of simulation data in any given study.
Grossfield
Alan
A
University of Rochester Medical Center, Department of Biochemistry and Biophysics, Box 712, Rochester, N.Y., 14642, USA, 585-276-4193.
Zuckerman
Daniel M
DM
J Chem Theory Comput. 2008 Apr;4(4):626-36
26620937
J Phys Chem B. 2005 May 12;109(18):9096-103
16852082
Biophys J. 2006 Jul 1;91(1):164-72
16617086
Proteins. 2002 Aug 15;48(3):487-96
12112673
Phys Rev Lett. 1992 Apr 27;68(17):2696-2699
10045464
Proteins. 2007 Apr 1;67(1):31-40
17243153
J Chem Theory Comput. 2007 Jan;3(1):26-41
26627148
Biopolymers. 1984 Jun;23(6):1099-112
6733249
J Chem Theory Comput. 2006 Nov;2(6):1693
26627040
J Chem Phys. 2007 Apr 21;126(15):155101
17461665
Nature. 1977 Jun 16;267(5612):585-90
301613
Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Mar;65(3 Pt 1):031910
11909112
J Chem Phys. 2005 Apr 8;122(14):144107
15847516
J Phys Chem B. 2007 Nov 8;111(44):12876-82
17935314
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1996 Apr;53(4):3682-3693
9964678
J Comput Chem. 2007 Nov 15;28(14):2309-16
17476669
J Mol Biol. 2008 Aug 29;381(2):478-86
18585736
Proteins. 1995 Aug;22(4):311-21
7479706
Proteins. 2004 Dec 1;57(4):783-91
15317024
Phys Rev Lett. 1986 Nov 24;57(21):2607-2609
10033814
Phys Rev A. 1990 Oct 15;42(8):4574-4587
9904563