Docking Server

Infobox Software
name = Docking Server
developer = Virtua Drug Ltd
latest_release_version = 1.0
latest_release_date = June 26, 2008
operating_system = web operating system
genre = Molecular modelling
website = [http://www.dockingserver.com/ Docking Server web site]

Docking Server is a web-based interface that handles molecular docking, from ligand and protein set-up through results representation integrating a number of software frequently used in computational chemistry. The application can be used for docking and analysis of single ligands as well as for high throughput docking of ligand libraries to target proteins.

Introduction

Analysis of the mode of interaction between ligands and their target proteins is of crucial importance in order to explore different aspects of biochemical processes. Besides laboratory experiments, there is an emerging role of in-silico methods in investigating the interactions of ligands to proteins. In-silico study of protein-ligand interaction involves molecular docking, where the binding energy and geometry of ligands, substrates or possible drug candidates to target proteins is predicted using computational chemistry methods.The task in molecular docking assignments is to find the best protein-ligand complex geometry. The problem is usually seen as an optimization task where the goal is to minimize the intermolecular interaction energy between the two molecules of interest. Since the possible number of protein-ligand complex geometry is usually very large, different algorithms are used in order to accurately explore the space of possible conformations while decreasing the computational power needed for the docking calculation at the same time. Thus, a molecular docking calculation consists of the following steps: (1) optimization of the ligand geometry, calculate pH-dependent partial charges, identify rotatable bonds and (2) calculate electrostatic properties of the protein of interest and define the ligand-binding region, (3) the ligand-protein interaction is then calculated by a scoring function that includes terms and equations that describe the intermolecular energies. The result of a docking calculation is a ligand-protein complex geometry and the corresponding binding energy. Therefore, for accurate interpretation of the results, a high-quality representation of the complex geometry is of great importance as well (4).

Description

DockingServer integrates a number of computational chemistry software specifically aimed at correctly calculating parameters needed at different steps of the docking procedure, i.e. accurate ligand geometry optimization, energy minimization, charge calculation, docking calculation and protein-ligand complex representation. Thus, the use of DockingServer allows the user to carry out highly efficient and robust docking calculation, which could not be achieved using single software so far. Since the calculations run on the servers, the use of DockingServer does not require powerful hardware or pre-installed software from the user.The core of DockingServer web application is our integrating PHP software connected to a database, where the different tasks are automatically managed by daemons running on our servers and the input data will be read from the database and output data will be directed into the database.

The AutoGrid/AutoDock 4.0 cite journal|author= Morris, G.M., Goodsell, D.S., Halliday, R.S., Huey, R., Hart, W.E., Belew, R.K. and Olson, A.J.| title=Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function journal=Journal Of Computational Chemistry|date=1998| volume=19 |pages=1639-1662 ] program package is used for docking calculations, allowing docking of flexible ligands to proteins. With the help of Autodock program package the partial charges and atom types of the ligand and proteins can be assigned. However, the results of docking calculations strongly depend on the accuracy of charges calculated in the ligand. Thus, besides offering ligand partial charge calculation with the AutoDock program package DockingServer also integrates calculator plug-ins from Chemaxon cite journal|author= Csizmadia F| title=JChem: Java applets and modules supporting chemical database handling from web browsers| journal=Journal of Chemical Information and Computer Sciences|date=2000| volume=40 |pages=323-324 ] and the MOPAC2007 program (Stewart, 2007) for accurate pH-dependent protonation and ligand partial charge calculation. Moreover, geometry optimization, refinement of the ligand geometry using semiempirical methods (PM6) can be carried out. Automatic conversions between necessary file formats are achieved by Chemaxon tools.For representation of the resulted protein-ligand complexes, Jmol [http://jmol.sourceforge.net] and [VMD] (Humphrey, et al., 1996) are integrated in Docking Server, which provide a wide range of molecular representations, coloring styles, transparency and material properties. For drawing and presenting ligands, Marvin Sketch from Chemaxon is used.

References