Enhanced sampling reveals the main pathway of an organic cascade reaction

Abstract

Normal molecular dynamics simulations are usually unable to simulate chemical reactions due to the low probability of forming the transition state. Therefore, enhanced sampling methods are implemented to accelerate the occurrence of chemical reactions. In this investigation, we present an application of metadynamics in simulating an organic multi-step cascade reaction. The analysis of the reaction trajectory reveals the barrier heights of both forward and reverse reactions. We also present a discussion of the advantages and disadvantages of generating the reactive pathway using molecular dynamics and the intrinsic reaction coordinate (IRC) algorithm.