Combining Structural Data with Computational Methodologies to Investigate Structure–Function Relationships in TRP Channels

Since the emergence of high-resolution three-dimensional structures of membrane proteins, and the increasing availability of state-of-the-art algorithms and high-performance-computing facilities, classical molecular dynamics (MD) simulations have become a routine device to explore the molecular behavior of these proteins. The rise of cryo-electron microscopy (cryo-EM) as a credible experimental tool to resolve structures at an atomic level has revolutionized structural biology in recent years, culminating in the disclosure of the first high-resolution three-dimensional structure of a transient receptor potential (TRP) channel, the vanilloid receptor 1 (TRPV1). As a result, the number of research articles investigating the molecular behavior of TRP channels using macromolecular simulation techniques has proliferated. This review provides an overview of the current state of this field, including our understanding of TRP channel structure, the framework of classical MD simulations, and how to perform such simulations to investigate structure-function relationships in TRP channels