Accelerating All-Atom Simulations and Gaining Mechanistic Understanding of Biophysical Systems through State Predictive Information Bottleneck

J Chem Theory Comput. 2022 May 10;18(5):3231-3238. doi: 10.1021/acs.jctc.2c00058. Epub 2022 Apr 6.

Abstract

An effective implementation of enhanced sampling algorithms for molecular dynamics simulations requires a priori knowledge of the approximate reaction coordinate describing the relevant mechanisms in the system. In this work, we focus on the recently developed artificial intelligence-based State Predictive Information Bottleneck (SPIB) approach and demonstrate how SPIB can learn such a reaction coordinate as a deep neural network even from undersampled trajectories. We exemplify its usefulness by achieving more than 40 times acceleration in simulating two model biophysical systems through well-tempered metadynamics performed by biasing along the SPIB-learned reaction coordinate. These include left- to right-handed chirality transitions in a synthetic helical peptide (Aib)9 and permeation of a small benzoic acid molecule through a synthetic, symmetric phospholipid bilayer. In addition to significantly accelerating the dynamics and achieving back and forth movement between different metastable states, the SPIB-based reaction coordinate gives mechanistic insights into the processes driving these two important problems.

MeSH terms

  • Artificial Intelligence*
  • Molecular Dynamics Simulation*
  • Peptides
  • Phospholipids
  • Thermodynamics

Substances

  • Peptides
  • Phospholipids