Effective Molecular Dynamics from Neural Network-Based Structure Prediction Models.

Abstract

Recent breakthroughs in neural network-based structure prediction methods, such as AlphaFold2 and RoseTTAFold, have dramatically improved the quality of computational protein structure prediction. These models also provide statistical confidence scores that can estimate uncertainties in the predicted structures, but it remains unclear to what extent these scores are related to the intrinsic conformational dynamics of proteins. Here, we compare AlphaFold2 prediction scores with explicit large-scale molecular dynamics simulations of 28 one- and two-domain proteins with varying degrees of flexibility. We demonstrate a strong correlation between the statistical prediction scores and the explicit motion derived from extensive atomistic molecular dynamics simulations and further derive an elastic network model based on the statistical scores of AlphFold2 (AF-ENM), which we benchmark in combination with coarse-grained molecular dynamics simulations. We show that our AF-ENM method reproduces the global protein dynamics with improved accuracy, providing a powerful way to derive effective molecular dynamics using neural network-based structure prediction models.