Small molecule recognition: solid angles surface representation and molecular shape complementarity.

TL;DR: Dock 185 receptor-small ligand molecule pairs and find that such a representation performs adequately for the smaller ligands too, and that shape complementarity is also observed.

Abstract: Here we examine the recognition of small molecules by their protein and DNA receptors. We focus on two questions: First, how well does the solid angle molecular surface representation perform in fitting together the surfaces of small ligands, such as drugs and cofactors to their corresponding receptors; And second, in particular, to what extent does the shape complementarity play a role in the matching (recognition) process of such small molecules. Both questions have been investigated in protein-protein binding: "Critical Points" based on solid angle calculations have been shown to perform well in the matching of large protein molecules. They are robust, may be few in numbers, and capture satisfactorily the molecular shape. Shape complementarity has been shown to be a critical factor in protein-protein recognition, but has not been examined in drug-receptor recognition. To probe these questions, here we dock 185 receptor-small ligand molecule pairs. We find that such a representation performs adequately for the smaller ligands too, and that shape complementarity is also observed. These issues are important, given the large databases of drugs that routinely have to be scanned to find candidate, lead compounds. We have been able to carry out such large scale docking experiments owing to our efficient, computer-vision based docking algorithms. Its fast CPU matching times, on the order of minutes on a PC, allows such large scale docking experiments.