High-Throughput Computation of Anharmonic Low-Frequency Protein Vibrations

TL;DR

This paper introduces a computationally efficient method combining coarse-graining with FRESEAN mode analysis to study anharmonic low-frequency vibrations in proteins, aiding conformational sampling.

Contribution

It presents a novel approach that reduces computational cost of FRESEAN mode analysis for large biomolecules by integrating coarse-graining techniques.

Findings

Coarse-graining enables analysis of large biomolecules with minimal computational resources.

FRESEAN mode analysis effectively isolates anharmonic low-frequency vibrations.

The method enhances conformational sampling in protein simulations.

Abstract

At room temperature, low frequency vibrations at far-infrared frequencies are thermally excited ($k_B T > h \nu$) and not restricted to harmonic fluctuations around a single potential energy minimum. For folded proteins, these intrinsically anharmonic vibrations can contain information on slow conformational transitions. Recently, we have developed FREquency-SElective ANharmonic (FRESEAN) mode analysis, a method based on time correlation functions that isolates low-frequency vibrational motions from molecular dynamics simulation trajectories without relying on harmonic approximations. We recently showed that low-frequency vibrations obtained from FRESEAN mode analysis are effective collective variables in enhanced sampling simulations of conformational ensembles. However, FRESEAN mode analysis is based on velocity time correlations between all degrees of freedom, which creates computational challenges for large biomolecules. To facilitate future applications, we demonstrate here how coarse-graining of all-atom simulation trajectories can be combined with FRESEAN mode analysis to extract information on low-frequency vibrations at minimal computational cost.