Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics

Investigation of macromolecular structure and dynamics is fundamental to understanding how macromolecules carry out their functions in the cell. Significant advances have been made toward this end in silico, with a growing number of computational methods proposed yearly to study and simulate various aspects of macromolecular structure and dynamics. This review aims to provide an overview of recent advances, focusing primarily on methods proposed for exploring the structure space of macromolecules in isolation and in assemblies for the purpose of characterizing equilibrium structure and dynamics. In addition to surveying recent applications that showcase current capabilities of computational methods, this review highlights state-of-the-art algorithmic techniques proposed to overcome challenges posed in silico by the disparate spatial and time scales accessed by dynamic macromolecules. This review is not meant to be exhaustive, as such an endeavor is impossible, but rather aims to balance breadth and depth of strategies for modeling macromolecular structure and dynamics for a broad audience of novices and experts.Author Summary: This paper provides an overview of recent advancements in computational methods for modeling macromolecular structure and dynamics. The focus is on methods aimed at providing efficient representations of macromolecular structure spaces for the purpose of characterizing equilibrium dynamics. The overview is meant to provide a summary of state-of-the-art capabilities of these methods from an application point of view, as well as highlight important algorithmic contributions responsible for recent advances in macromolecular structure and dynamics modeling.