An Introduction to Biomolecular Simulations and Docking

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.

The text is accompanied by 6 figures and 5 boxes. The text is in press at Molecular Simulation (2014), as part of a special issue on simulations in molecular biology

References in corpus (4)

• Replica exchange molecular dynamics simulations of amyloid peptide aggregation
• Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized
• Molecular Dynamics of a kB DNA Element: Base Flipping via Cross-strand Intercalative Stacking in a Microsecond-scale Simulation
• How interface geometry dictates water's thermodynamic signature in hydrophobic association

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• Reproducing Quantum Probability Distributions at the Speed of Classical Dynamics: A New Approach for Developing Force-Field Functors