PRODOCK: Software package for protein modeling and docking

A new software package, PRODOCK, for protein modeling and flexible docking is presented. The protein system is described in internal coordinates with an arbitrary level of flexibility for the proteins or ligands. The protein is represented by an all-atom model with the ECEPP/3 or AMBER IV force fiel d, depending on whether the Ligand is a peptidic molecule or not. PRODOCK i s based on a new residue data dictionary that makes the programming easier and the definition of molecular flexibility more straigthforward. Two versi ons of the dictionary have been constructed for the ECEPP/3 and AMBER IV ge ometry, respectively. The global optimization of the energy function is car ried out with the scaled collective variable Monte Carlo method plus energy minimization. The incorporation of a local minimization during the conform ational sampling has been shown to be very important for distinguishing low -energy normative conformations from native structures. To make the Monte C arlo minimization method efficient for docking, a new grid-based energy eva luation technique using Bezier splines has been incorporated. This article includes some techniques and simulation tools that significantly improve th e efficiency of flexible docking simulations, in particular forward/backwar d polypeptide chain generation. A comparative study to illustrate the advan tage of using quaternions over Euler angles for the rigid-body rotational v ariables is presented in this paper. Several applications of the program PR ODOCK are also discussed. (C) 1999 John Wiley & Sons, Inc.