Flooding in GROMACS: accelerated barrier crossings in molecular dynamics.
The major bottleneck of today's atomistic molecular dynamics (MD) simulations is that because of the enormous computational effort involved, only processes at nanoseconds to microseconds time scales or faster can be studied directly. Unfortunately, apart from a few exceptions, relevant processes, such as chemical reactions or many large scale conformational transitions in proteins, occur at slower time scales and therefore are currently far out of reach for conventional MD. The flooding technique addresses this problem by inclusion of a flooding potential into the force field. This flooding potential locally destabilizes the educt state and thereby significantly accelerates the escape from the initial energy well without affecting the reaction pathway. Here, we summarize the theory and method for the computational chemistry community and detail the implementation within the official version 3.3 of the freely available MD program package GROMACS. Two examples shall demonstrate the application of flooding to accelerate conformational transitions and chemical reactions. The second example was carried out within a QM/MM framework.
Lange
Oliver F
OF
Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Schäfer
Lars V
LV
Grubmüller
Helmut
H
D002073:Butanes / Q000737:chemistry; D003198:Computer Simulation; D003521:Cyclopropanes / Q000737:chemistry; D008956:Models, Chemical; D011789:Quantum Theory; D012984:Software; D013997:Time Factors
D002073:Butanes; D003521:Cyclopropanes; C046888:butane