Here we carry out an examination of shape complementarity as a criterion in protein--protein docking and binding. Specifically, we examine the quality of shape complementarity as a critical determinant not only in the docking of 26 protein--protein "bound", complexed cases, but in particular, of 19 "unbound" protein--protein cases, where the structures have been determined separately. In all cases, entire molecular surfaces are utilized in the docking, with no consideration of the location of the active site, or of particular residues/atoms in either the receptor or the ligand which participate in the binding. To evaluate the goodness of the strictly geometry-based shape complementarity in the docking process as compared to the main favorable and unfavorable energy components, we study systematically a potential correlation between each of these components and the RMSD of the "unbound" protein--protein cases. Specifically, we examine the non-polar buried surface area, polar b...

In this work we present an algorithm developed to handle biomolecular structural recognition problems, as part of an interdisciplinary research endeavor of the Computer Vision and Molecular Biology fields. A key problem is rational drug design and in biomolecular structural recognition is the generation of binding modes between two molecules, also known as molecular docking. Geometrical fitness is a necessary condition for molecular interaction. Hence, docking a ligand (e.g., a drug molecule or a protein molecule), to a protein receptor (e.g., enzyme), involves recognition of molecular surfaces. Conformational transitions by `hinge-bending' involves rotational movements of relatively rigid parts with respect to each other. The generation of docked binding modes between two associating molecules depends on their three dimensional structures (3-D) and their conformational flexibility. In comparison to the particular case of rigid-body docking, the computational difficulty grows considera...

We have developed and implemented a parallel distributed algorithm for the rigid-body protein docking problem. The algorithm is based on a new fitness function for evaluating the surface matching of a given conformation. The fitness function is defined as the weighted sum of two contact measures the geometric contact measure and the chemical contact measure. The geometric contact measure measures the "size" of the contact area of two molecules. It is a potential function that counts the "van der Waals contacts" between the atoms of the two molecules (the algorithm does not compute the Lennard-Jones potential). The chemical contact measure is also based on the "van der Waals contacts" principle: We consider all atom pairs that have a "van der Waals" contact, but instead of adding a constant for each pair (a; b) we add a "chemical weight" that depends on the atom pair (a; b). We tested our docking algorithm with a test set that contains the test examples of Norel et al. [NLWN94] and Fisc...