On the Effect of the Various Assumptions and Approximations used in Molecular Simulations on the Properties of Bio‐Molecular Systems: Overview and Perspective on Issues

Computer simulations of molecular systems enable structure‐energy‐function relationships of molecular processes to be described at the sub‐atomic, atomic, supra‐atomic or supra‐molecular level and plays an increasingly important role in chemistry, biology and physics. To interpret the results of such simulations appropriately, the degree of uncertainty and potential errors affecting the calculated properties must be considered. Uncertainty and errors arise from (1) assumptions underlying the molecular model, force field and simulation algorithms, (2) approximations implicit in the interatomic interaction function (force field), or when integrating the equations of motion, (3) the chosen values of the parameters that determine the accuracy of the approximations used, and (4) the nature of the system and the property of interest. In this overview, advantages and shortcomings of assumptions and approximations commonly used when simulating bio‐molecular systems are considered. What the developers of bio‐molecular force fields and simulation software can do to facilitate and broaden research involving bio‐molecular simulations is also discussed. In computer simulations of molecular systems, uncertainty and errors arise from (1) assumptions underlying the molecular model, force field and simulation algorithms, (2) approximations implicit in the force field or when integrating the equations of motion, (3) the chosen values of the parameters that determine the accuracy of the approximations used, and (4) the nature of the system and the property of interest. Advantages and shortcomings of assumptions and approximations commonly used are considered.