Validation of Molecular Simulation: An Overview of Issues

Abstract 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 Q exp of experimentally observable quantities Q . One must consider 1) the accuracy of Q exp , 2) the accuracy of the function Q( r N ) used to calculate a Q ‐value based on a molecular configuration r N of N particles, 3) the sensitivity of the function Q( r N ) to the configuration r N , 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.