On the calculation of equilibrium thermodynamic properties from molecular dynamics.

The purpose of statistical mechanics is to provide a route to the calculation of macroscopic properties of matter from their constituent microscopic components. It is well known that the macrostates emerge as ensemble averages of microstates. However, this is more often stated than implemented in computer simulation studies. Here we consider foundational aspects of statistical mechanics which are overlooked in most textbooks and research articles that purport to compute macroscopic behaviour from microscopic descriptions based on classical mechanics and show how due attention to these issues leads in directions which have not been widely appreciated in the field of molecular dynamics simulation.

[1]  P. Baert.  Time in contemporary intellectual thought , 2000 .

[2]  Shantenu Jha,et al.  Computing Clinically Relevant Binding Free Energies of HIV-1 Protease Inhibitors , 2014, Journal of chemical theory and computation.

[3]  Berend Smit,et al.  Understanding molecular simulation: from algorithms to applications , 1996 .

[4]  Kevin Barraclough,et al.  I and i , 2001, BMJ : British Medical Journal.

[5]  Achim Klenke,et al.  Probability theory - a comprehensive course , 2008, Universitext.

[6]  David Ruelle,et al.  Thermodynamic Formalism: The Mathematical Structure of Equilibrium Statistical Mechanics , 2004 .

[7]  Charlotte M. Deane,et al.  Rapid, Precise, and Reproducible Prediction of Peptide-MHC Binding Affinities from Molecular Dynamics That Correlate Well with Experiment. , 2015, Journal of chemical theory and computation.

[8]  P. Coveney,et al.  Canonical nonequilibrium ensembles and subdynamics , 1994 .

[9]  A. Elofsson,et al.  How consistent are molecular dynamics simulations? Comparing structure and dynamics in reduced and oxidized Escherichia coli thioredoxin. , 1993, Journal of molecular biology.

[10]  P. Coveney,et al.  From base pair to bedside: molecular simulation and the translation of genomics to personalized medicine , 2012, Wiley interdisciplinary reviews. Systems biology and medicine.

[11]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[12]  H. Reichenbach,et al.  The Direction of Time , 1959 .

[13]  M. Karplus,et al.  Locally accessible conformations of proteins: Multiple molecular dynamics simulations of crambin , 1998, Protein science : a publication of the Protein Society.

[14]  Peter V. Coveney,et al.  Accurate Ensemble Molecular Dynamics Binding Free Energy Ranking of Multidrug-Resistant HIV-1 Proteases , 2010, J. Chem. Inf. Model..

[15]  I. Prigogine,et al.  From Being to Becoming: Time and Complexity in the Physical Sciences , 1982 .

[16]  O. Penrose,et al.  Is there a ‘canonical’ non-equilibrium ensemble? , 1994, Proceedings of the Royal Society of London. Series A: Mathematical and Physical Sciences.

[17]  P. Coveney,et al.  Mechanism of Drug Efficacy Within the EGF Receptor Revealed by Microsecond Molecular Dynamics Simulation , 2012, Molecular Cancer Therapeutics.

[18]  O. Penrose,et al.  On the validity of the Brussels formalism in statistical mechanics , 1992 .

[19]  V. I. Arnolʹd,et al.  Ergodic problems of classical mechanics , 1968 .

[20]  P. Coveney,et al.  The arrow of time : a voyage through science to solve time's greatest mystery , 1991 .

[21]  S. Hawking.  A Brief History of Time: From the Big Bang to Black Holes , 1988 .

[22]  Albert C. Pan,et al.  Transitions to catalytically inactive conformations in EGFR kinase , 2013, Proceedings of the National Academy of Sciences.

[23]  R. Balescu.  Equilibrium and Nonequilibrium Statistical Mechanics , 1991 .

[24]  P. Coveney,et al.  The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study , 2015, EBioMedicine.

[25]  Albert C. Pan,et al.  Molecular determinants of drug-receptor binding kinetics. , 2013, Drug discovery today.

[26]  Roger Penrose,et al.  A complete guide to the laws of the universe , 2005 .

[27]  Peter V Coveney,et al.  Rapid and accurate ranking of binding affinities of epidermal growth factor receptor sequences with selected lung cancer drugs , 2011, Journal of The Royal Society Interface.