Determining equilibrium constants for dimerization reactions from molecular dynamics simulations

Abstract: With today’s available computer power, free energy calculations from equilibrium molecular dynamics simulations “via counting” become feasible for an increasing number of reactions. An example is the dimerization reaction of transmembrane alpha-helices. If an extended simulation of the two helices covers sufficiently many dimerization and dissociation events, their binding free energy is readily derived from the fraction of time during which the two helices are observed in dimeric form. Exactly how the correct value for the free energy is to be calculated, however, is unclear, and indeed several different and contradictory approaches have been used. In particular, results obtained via Boltzmann statistics differ from those determined via the law of mass action. Here, we develop a theory that resolves this discrepancy. We show that for simulation systems containing two molecules, the dimerization free energy is given by a formula of the form G ∝ ln(P1/P0). Our theory ...

• Type: Journal
• Year: 2011
• Where: JCC
• Authors: Djurre H. De Jong, Lars V. Schäfer, Alex H. De Vries, Siewert J. Marrink, Herman J. C. Berendsen, Helmut Grubmüller
• Keywords: Free Energy, JCC 2011, Molecular Dynamics Simulations, Simulations