Reformulation of the self-guided molecular simulation method.

Abstract

Self-guided molecular/Langevin dynamics (SGMD/SGLD) simulation methods were developed to enhance conformational sampling through promoting low frequency motion of molecular systems and have been successfully applied in many simulation studies. Quantitative understanding of conformational distribution in SGLD has been achieved by separating microscopic properties according to frequency. However, a missing link between the guiding factors and conformational distributions makes it highly empirical and system dependent when choosing the values of the guiding parameters. Based on the understanding that molecular interactions are the source of energy barriers and diffusion friction, this work reformulates the equation of the low frequency motion to resemble Langevin dynamics. This reformulation leads to new forms of guiding forces and establishes a relation between the guiding factors and conformational distributions. We call simulations with these new guiding forces the generalized self-guided molecular/Langevin dynamics (SGMDg/SGLDg). In addition, we present a new way to calculate low frequency properties and an efficient algorithm to implement SGMDg/SGLDg that minimizes memory usage and inter-processor communication. Through example simulations with a skewed double well system, an argon fluid, and a cryo-EM map flexible fitting case, we demonstrate the guiding effects on conformational distributions and conformational searching.