2024/03/18 by Souvik Mondal, Mondal, Souvik, Michael A. Sauer +3 · 1 citation
Engineering · #Dynamics and Control of Mechanical Systems #FOS: Physical sciences #Statistical Mechanics (cond-mat.stat-mech)
paper · pdf · doi:10.48550/arxiv.2403.12174
openalex publication_date 2024/03/18 · openalex created_date 2024/03/21 · openalex updated_date 2026/07/28
We aim to automatize the identification of collective variables to simplify and speed up enhanced sampling simulations of conformational dynamics in biomolecules. We focus on anharmonic low-frequency vibrations that exhibit fluctuations on timescales faster than conformational transitions but describe a path of least resistance towards structural change. A key challenge is that harmonic approximations are ill-suited to characterize these vibrations, which are observed at far-infrared frequencies and are easily excited by thermal collisions at room temperature. Here, we approached this problem with a frequency-selective anharmonic (FRESEAN) mode analysis that does not rely on harmonic approximations and successfully isolates anharmonic low-frequency vibrations from short molecular dynamics simulation trajectories. We applied FRESEAN mode analysis to simulations of alanine dipeptide, a common test system for enhanced sampling simulation protocols, and compare the performance of isolated low-frequency vibrations to conventional user-defined collective variables (here backbone dihedral angles) in enhanced sampling simulations. The comparison shows that enhanced sampling along anharmonic low-frequency vibrations not only reproduces known conformational dynamics but can even further improve sampling of slow transitions compared to user-defined collective variables. Notably, free energy surfaces spanned by low-frequency anharmonic vibrational modes exhibit lower barriers associated with conformational transitions relative to representations in backbone dihedral space. We thus conclude that anharmonic low-frequency vibrations provide a promising path for highly effective and fully automated enhanced sampling simulations of conformational dynamics in biomolecules.