Sense and nonsense when performing and interpreting molecular dynamics simulations of biomolecular systems Wilfred F. van Gunsteren Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, 8093 Zurich, Switzerland Computer simulation of the dynamics of biomolecular systems by the molecular dynamics technique yields the possibility of describing structure-energy-function relationships of biomolecular processes in terms of interactions at the sub-atomic, atomic, supra-atomic or even supra-molecular level of resolution. The reliability and interpretability of different aspects of such simulations depends critically on (i) the degrees of freedom simulated, (ii) the type of model and inter-particle interactions or force field used and its calibration, (iii) whether a statistical-mechanical ensemble is generated or used in the averaging to obtain values of quantities of interest, and (iv) on the way the spatial and thermodynamic boundary conditions of the finite system are modelled. Since the first biomolecular simulations carried out during the 1970-ies, a variety of models, force fields and algorithms have been proposed, of which some have found general use. Amongst the latter are reliable, efficient ones, but also models and procedures that introduce bias into a simulation or are statistical-mechanically or energetically less sound, thereby impairing the interpretability of the simulated set of biomolecular configurations. Recent examples of such cases will be discussed. W.F. van Gunsteren, “On testing theoretical models by comparison of calculated with experimental data”, in: Studies in Physical and Theoretical Chemistry, Vol. 71, J.L. Rivail ed., Elsevier, Amsterdam, 1990, 463-478 W.F. van Gunsteren et al., “Computer simulation of protein motion”, Computer Physics Communications 91 (1995) 305-319 W.F. van Gunsteren and A.E. Mark, “Validation of molecular dynamics simulation”, J. Chem. Phys. 108 (1998) 6109-6116 W.F. van Gunsteren and J. Dolenc, “Biomolecular simulation: historical picture and future perspectives”, Biochem. Soc. Trans. 36 (2008) 11-15 W.F. van Gunsteren and J. Dolenc, “Thirty-five years of biomolecular simulation: development of methodology, force fields and software”, Mol. Sim. 38 (2012) 1271-1281 W.F. van Gunsteren, “The seven sins in academic behaviour in the natural sciences”, Angew. Chem. Int. Ed. 52 (2013) 118-122 www.igc.ethz.ch and www.gromos.net

Sense and nonsense when performing and interpreting molecular dynamics simulations of biomolecular systems

249th National Meeting (2015)

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