Survey of public domain software for docking simulations and virtual screening

Docking simulations and virtual screening are being routinely used in drug design, enabling rapid identification of hits and lead compounds [1-3]. The goal of docking simulations is to determine the binding mode (bound conformation) and the strength of binding (binding affinity) between a ligand, which is typically assumed to be a small molecule, and a macromolecular receptor, such as a protein [1,3,4]. Given a resolved or modelled structure of a target receptor, virtual screening involves performing docking simulations for a large number of candidate compounds in order to identify putative leads [2,5,6]. These candidates can subsequently be characterised and validated by empirical binding and activity assays, and by assessing their toxicity, pharmacokinetics and other properties for further drug development [7-9].Many methods for molecular docking and virtual screening have been developed to date, including AutoDock,[10,11] DOCK,[12-14] Flex,[15] Glide,[16] GOLD,[17] RosettaDock,[18] SLIDE [19,20] and Surflex [21]. These methods introduce various approximations to simplify the problem -- for example, assuming a rigid body docking model in which the receptor structure is fixed. Rigid body docking allows one to speed-up computations by comparison with flexible docking (in which the receptor structure is allowed to move) by precomputing the forces experienced by the ligand on a grid. In general, docking simulations involve two main components: sampling algorithms to find plausible conformations of the complex, and scoring functions to estimate relative binding affinities and rank ligand poses [1].The sampling of alternative conformation is coupled with the search for the optimal solution --that is, poses with the highest binding affinity (or score), which typically involves solving a global optimisation problem. Consequently, various optimisation techniques -- such as Monte Carlo, simulated annealing or genetic algorithms -- are used in the context of docking simulati