Digital metadynamics: New biased simulation concept and its testing on the conformational equilibrium of Ac-Ala-NHMe
Pavel Oborský, Vojtěch Spiwok
Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 3, Prague 6, 166 28, Czech Republic
According to the Moor's law, computer performance doubles every 18 month. Despite that the computer performance is the main limitation for simulation methods in chemistry. Various events occur in timescales larger than accessible through the computing. Instead of waiting for better computers, sophisticated methods are being developed to enhance efficiency of calculations, such as metadynamics. Metadynamics uses collective variables, which are relevant for the studied event, and during the simulation disfavours them with the bias potential in the manner the system is forced to escape from visited values of the collective variables. This causes faster sampling of molecule's conformations. The negative picture of inserted bias potential is the free energy surface in the space of collective variables. Improvement of metadynamics, called digital metadynamics, uses reference structures of the molecule instead of the collective variables. The bias potential is inserted during the simulation in reference structures based on similarity with the simulated molecule. Retroactively inserted bias potential influence dynamics of the molecule through repulsion from reference structures where the bias potential was added. For testing digital metadynamics, a model of peptide bond Ac-Ala-NHMe was used. The result was a Ramachandran plot in an agreement with the same plot obtained from classic metadynamics.