  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.
