Validation of Molecular Simulation: An Overview of Issues

• Published in: Angewandte Chemie International Edition Vol. 57; no. 4; pp. 884 - 902
• Main Authors: van Gunsteren, Wilfred F., Daura, Xavier, Hansen, Niels, Mark, Alan E., Oostenbrink, Chris, Riniker, Sereina, Smith, Lorna J.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 22.01.2018
• Edition: International ed. in English
• Subjects: Atomic structure; computer chemistry; Computer simulation; Configurations; experimental data; Mathematical analysis; molecular dynamics simulation; Molecular structure; Monte Carlo simulation; pseudo-validation; Structure-function relationships; pseudo-validation; Monte Carlo simulation; experimental data; computer chemistry; molecular dynamics simulation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201702945

Computer simulation of molecular systems enables structure–energy–function relationships of molecular processes to be described at the sub‐atomic, atomic, supra‐atomic, or supra‐molecular level. To interpret results of such simulations appropriately, the quality of the calculated properties must be evaluated. This depends on the way the simulations are performed and on the way they are validated by comparison to values Qexp of experimentally observable quantities Q. One must consider 1) the accuracy of Qexp, 2) the accuracy of the function Q(rN) used to calculate a Q‐value based on a molecular configuration rN of N particles, 3) the sensitivity of the function Q(rN) to the configuration rN, 4) the relative time scales of the simulation and experiment, 5) the degree to which the calculated and experimental properties are equivalent, and 6) the degree to which the system simulated matches the experimental conditions. Experimental data is limited in scope and generally corresponds to averages over both time and space. A critical analysis of the various factors influencing the apparent degree of (dis)agreement between simulations and experiment is presented and illustrated using examples from the literature. What can be done to enhance the validation of molecular simulation is also discussed. Assumptions, approximations, and pitfalls: Validation of the results of molecular simulations is a process beset with theoretical and practical problems. The effects of the various assumptions and approximations involved in the formulation of a molecular model and its simulation and the pitfalls of comparing simulated with experimental data are discussed. Ways to enhance validation of molecular simulation are suggested.