DOCKER, an interactive program for simulating protein receptor and substrate interactions

A computer graphics program written for the Evans & Sutherland Picture System 2 allows the interactive docking of a flexible polypeptide into a protein receptor of known three-dimensional structure. Both can be described as either van der Waals or accessible surfaces and a cleft or receptor site can be described as an accessible volume. The program indicates disallowed intermolecular contacts during the docking process, and will also calculate surface-accessible areas and the energy of the system. A non-interactive process of energy refinement can be activated at any time by the user. The program has been used to fit a peptide substrate to the structure of an enzyme, an aspartate proteinase, which has a deep and extended cleft known to be involved in substrate binding. The program is of general value in exploring the complementarity of peptides, which are possible substrates or inhibitors, to proteins whose structures have been defined by X-ray analysis-a process of great importance in rational drug design.