Thirty years of molecular dynamics simulations on posttranslational modifications of proteins

TL;DR

This paper reviews thirty years of molecular dynamics simulations to understand how posttranslational modifications alter protein structure and function, highlighting past progress and future research opportunities with current computational advancements.

Contribution

It provides a comprehensive overview of the history, methodologies, and insights gained from molecular dynamics studies on PTMs over the past three decades.

Findings

Different timescales reveal diverse PTM effects

Analysis approaches influence interpretation of PTM impacts

Modern computational capabilities enable advanced PTM research

Abstract

Posttranslational modifications (PTMs) are an integral component to how cells respond to perturbation. While experimental advances have enabled improved PTM identification capabilities, the same throughput for characterizing how structural changes caused by PTMs equate to altered physiological function has not been maintained. In this Perspective, we cover the history of computational modeling and molecular dynamics simulations which have characterized the structural implications of PTMs. We distinguish results from different molecular dynamics studies based upon the timescales simulated and analysis approaches used for PTM characterization. Lastly, we offer insights into how opportunities for modern research efforts on in silico PTM characterization may proceed given current state-of-the-art computing capabilities and methodological advancements.