Bias‐exchange metadynamics applied to the study of chemical reactivity

Abstract We show how the combination of Bias Exchange metadynamics (BE) with Car‐Parrinello molecular dynamics (CPMD) can lead to vast improvements in the study of chemical reactions. Bias Exchange metadynamics is a recently introduced methodology that combines replica exchange techniques with the metadynamics approach. It allows fast parallel reconstruction of the free energy of a system in a virtually unlimited number of variables. The value of the method was previously demonstrated for the folding of a Triptophane cage miniprotein on the classical potential energy surface. As a test case for the DFT implementation, we investigated the competitive S N 2 reaction of CH 3 Cl with Cl − and Br − . The results illustrate three important advantages of the method. (1) Fast and complete sampling of configuration space occurs in each replica. (2) A significant speed‐up can be observed in the convergence of the free energy profiles, compared with regular metadynamics. (3) The best conformational distributions are successfully transferred from one replica to the others. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2010