On the importance of statistics in molecular simulations for thermodynamics, kinetics and simulation box size

• Published in: eLife Vol. 9
• Main Authors: Gapsys, Vytautas, de Groot, Bert L
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications, Ltd 19.08.2020; eLife Sciences Publications Ltd
• Subjects: Biometry; Biostatistics - methods; Computer Simulation; Kinetics; molecular dynamics; Molecular Dynamics Simulation; Protein Conformation; simulation; statistics; Structural Biology and Molecular Biophysics; Thermodynamics; Tools and Resources; simulation; thermodynamics; structural biology; none; kinetics; molecular biophysics; molecular dynamics; statistics
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.57589

Computational simulations, akin to wetlab experimentation, are subject to statistical fluctuations. Assessing the magnitude of these fluctuations, that is, assigning uncertainties to the computed results, is of critical importance to drawing statistically reliable conclusions. Here, we use a simulation box size as an independent variable, to demonstrate how crucial it is to gather sufficient amounts of data before drawing any conclusions about the potential thermodynamic and kinetic effects. In various systems, ranging from solvation free energies to protein conformational transition rates, we showcase how the proposed simulation box size effect disappears with increased sampling. This indicates that, if at all, the simulation box size only minimally affects both the thermodynamics and kinetics of the type of biomolecular systems presented in this work.