Efficiently finding the minimum free energy path from steepest descent path

Abstract

Minimum Free Energy Path (MFEP) is very important in computational biology and chemistry. The barrier in the path is related to the reaction rate, and the start-to-end difference gives the relative stability between reactant and product. All these information is significant to experiment and practical application. But finding MFEP is not an easy job. Lots of degrees of freedom make the computation very complicated and time consuming. In this paper, we use the Steepest Descent Path (SDP) to accelerate the sampling of MFEP. The SHAKE algorithm and the Lagrangian multipliers are used to control the optimization of both SDP and MFEP. These strategies are simple and effective. For the former, it is more interesting. Because as we known, SHAKE algorithm was designed to handle the constraints in molecular dynamics in the past, has never been used in geometry optimization. Final applications on ALA dipeptide and 10-ALA peptide show that this combined optimization method works well. Use the information in SDP, the initial path could reach the more optimal MFEP. So more accurate free energies could be obtained and the amount of computation time could be saved.