Description:Molecular docking simulations using AutoDock
Abstract:Docking simulation programs have significant potential to contribute to a wide area of molecular and biomedical research, assuming that the results of the simulation prove consistent with the outcome of conventional laboratory based experiments. AutoDock is one example of a program which allows in silico modelling of intermolecular interactions. Emerging literature shows that AutoDock can be successfully utilized in research strategies for the study of molecular interactions in cancer and for designing drug inhibitors for HIV, for example. A tailored modification of AutoDock provides useful information, particularly when taken in combination with conventional laboratory experiments, and allows researchers to draw conclusions from protein-ligand interactions.
AutoDock is a suite of automated docking tools. It is designed to predict how small molecules, such as substrates or drug candidates, bind to a receptor of known 3D structure. AutoDock currently comprises of two discrete generations of software: AutoDock 4 and AutoDock Vina. The latter provides several enhancements over the former, increasing average simulation accuracy whilst also being up to two orders of magnitude faster. Autodock Vina is particularly useful for virtual screening, whereby a large set of ligands can be compared for docking suitability with a single receptor. In this instance parallelism is achieved by first breaking the set of all ligands into equal sized disjoint subsets. Each compute job then uses a different subset as an input. The ligands in each subset are simulated/docked sequentially on the compute node using the single receptor, whilst a post processing stage can be used to compare the results from all compute jobs. AutoDock Vina has native Windows binaries, and requires only local file storage upon any compute nodes for storing both inputs and outputs.
AutoDock 4 is typically used to accurately model the molecular docking of a single ligand to a single receptor. In this instance the process is composed of 3 discrete stages. First a low complexity sequential pre-processing stage defines a random starting location in 3D space (termed the docking space) for both the ligand and receptor. This is achieved using a tool within AutoDockTools (ADT) called AutoGrid. The locations, which are characterised by atomic energy levels at each point within the docking space, act as a single common input to a second stage. The second stage can comprise many parallel jobs, each receiving a copy of the ligand and receptor starting locations which form the input to a genetic algorithm. The algorithm acts to randomly rotate/reposition the ligand and then determine likely docking/binding sites based upon energy levels which are calculated from the original starting locations. This process can be considered a parameter sweep, where the varied input parameter is the initial random rotation of the ligand. Finally, a single low complexity sequential post-processing stage can be used to identify the most likely binding sites by comparing energies from all jobs of the preceding stage (where minimized energies represent likely docking sites).
Both AutoDock 4.2.3 and AutoDock Vina 1.1.2 are available for production level utilization on BOINC based desktop grids. Workflows for running docking simulations are publicly available via science gateways. See also: the AutoDock Gateway (http://appdb.egi.eu/store/software/autodock.gateway) and the University of Westminster DG Portal (http://appdb.egi.eu/store/software/university.of.westminster.dg.portal).