MultiDock (v1.0)(Multiple copy side-chain refinement of Protein-Protein interfaces)
The program MultiDock was developed to provide a method for refining the interface between two proteins at the atomic level given an initial docked complex generated by a docking algorithm or manual docking procedure. The motivation for this work was to provide a rapid energy refinement protocol for the large number of putative docked complexes produced by rigid-body docking programs such as FTDock or DOCK. The program models the effects of side-chain conformational change and the rigid-body movement of the interacting proteins during refinement.
The protein is described at the atomic level by electrostatic and van der Waals interactions in which the sidechains are modelled by a multiple copy representation according to a rotamer library on a fixed peptide backbone. MultiDock implements the self consistent Mean Field Optimisation procedure (Koehl & Delarue 1994) but using a full conventional molecular mechanics force field with scaling of van der Waals and electrostatic interactions for unrealistically close atomic contacts. MultiDock also implements a rigid-body energy minimization routine which is performed to relax the interface.
MultiDock has been tested by performing refinement of large numbers of structures generated by FTDock on several protein-protein systems. The results are encouraging for Protein-Inhibitor systems. For a detailed description of the program and application to protein-protein systems see Jackson et al. 1998.
At present MultiDock is only available for SILICON GRAPHICS WORKSTATIONS or LINUX i386
The series of programs comprising MultiDock are available only as executables. They were developed under SGI Irix versions 5.3 and 6.2. The memory requirements for the present version of MultiDock is 61 Mb.
The main MultiDock algorithm uses a multiple copy representation of side chains. For each cycle of Mean Field Optimisation all residue-residue sidechain interactions (up to 300,000) are pre-calculated and stored by the program. This determines the memory requirements of the program since the fewer the number of residue-residue sidechain interactions the less memory is required. The number of sidechain interactions is controled by the extent of the protein-protein interface, the extent of the multiple copy region and the extended fixed boundary region surrounding it. Inputing the control parameters that control these factors are described in the MultiDock user-manual (PDF). The CPU times for several different sized systems are given in Jackson et al. 1998 for a SGI R10000 processor.
Run times on the SGI R4400 and R5000 processors are much longer. Provisional tests using a SGI R4400 processor would suggest CPU times increase by a factor of 2.5 to 3.