MOLECULAR RECOGNITION VIA FACE CENTER REPRESENTATION OF A MOLECULAR-SURFACE

While docking methodologies are now frequently being developed, a care ful examination of the molecular surface representation, which necessa rily is employed by them, is largely overlooked. There are two importa nt aspects here that need to be addressed: how the surface representat ion quantifies surface complementarity, and whether a minimal represen tation is employed. Although complementarity is an accepted concept re garding molecular recognition, its quantification for computation is n ot trivial, and requires verification. A minimal representation is imp ortant because docking searches a conformational space whose extent an d/or dimensionality grows quickly with the size of surface representat ion, making it especially costly with big molecules, imperfect interfa ces, and changes of conformation that occur in binding. It is essentia l for a docking methodology to establish that it employs an accurate, concise molecular surface representation. Here we employ the face cent er representation of molecular surface, developed by Lin et al.,(1) to investigate the complementarity of molecular interface. We study a wi de variety of complexes: protein/small ligand, oligomeric chain-chain interfaces, proteinase/protein inhibitors, antibody/antigen, NMR struc tures, and complexes built from unbound, separately solved structures. The complementarity is examined at different levels of reduction, and hence roughness, of the surface representation, from one that describ es subatomic details to a very sparse one that captures only the promi nent features on the surface. Our simulation of molecular recognition indicates that in all cases, quality interface complementarity is obta ined. We show that the representation is powerful in monitoring the co mplementarity either in its entirety, or in selected subsets that main tain a fraction of the face centers, and is capable of supporting mole cular docking at high fidelity and efficiency. Furthermore, we also de monstrate that the presence of explicit hydrogens in molecular structu res may not benefit docking, and that the different classes of protein complexes may hold slightly different degrees of interface complement arity.