An Introduction to Biomolecular Simulations and Docking

TL;DR

This paper introduces the principles and applications of biomolecular simulations and docking, emphasizing their role in understanding molecular interactions, structure, and dynamics in biological systems.

Contribution

It provides a comprehensive overview of the physical principles, algorithms, and recent advancements in molecular simulations and docking for biomolecular research.

Findings

Simulations enable detailed analysis of biomolecular structures and interactions.

Modern algorithms have made simulations more accessible and accurate.

Simulations are essential for studying cellular-scale biomolecular assemblies.

Abstract

The biomolecules in and around a living cell -- proteins, nucleic acids, lipids, carbohydrates -- continuously sample myriad conformational states that are thermally accessible at physiological temperatures. Simultaneously, a given biomolecule also samples (and is sampled by) a rapidly fluctuating local environment comprised of other biopolymers, small molecules, water, ions, etc. that diffuse to within a few nanometers, leading to inter-molecular contacts that stitch together large supramolecular assemblies. Indeed, all biological systems can be viewed as dynamic networks of molecular interactions. As a complement to experimentation, molecular simulation offers a uniquely powerful approach to analyze biomolecular structure, mechanism, and dynamics; this is possible because the molecular contacts that define a complicated biomolecular system are governed by the same physical principles (forces, energetics) that characterize individual small molecules, and these simpler systems are relatively well-understood. With modern algorithms and computing capabilities, simulations are now an indispensable tool for examining biomolecular assemblies in atomic detail, from the conformational motion in an individual protein to the diffusional dynamics and inter-molecular collisions in the early stages of formation of cellular-scale assemblies such as the ribosome. This text introduces the physicochemical foundations of molecular simulations and docking, largely from the perspective of biomolecular interactions.