Taking geometry to its edge: Fast unbound rigid (and hinge‐bent) docking

Abstract

We present a very efficient rigid "unbound" soft docking methodology, which is based on detection of geometric shape complementarity, allowing liberal steric clash at the interface. The method is based on local shape feature matching, avoiding the exhaustive search of the 6D transformation space. Our experiments at CAPRI rounds 1 and 2 show that although the method does not perform an exhaustive search of the 6D transformation space, the "correct" solution is never lost. However, such a solution might rank low for large proteins, because there are alternatives with significantly larger geometrically compatible interfaces. In many cases this problem can be resolved by successful a priori focusing on the vicinity of potential binding sites as well as the extension of the technique to flexible (hinge-bent) docking. This is demonstrated in the experiments performed as a lesson from our CAPRI experience.

Resveratrol acts as a topoisomerase II poison in human glioma cells

“…Docking simulations of RSV onto TOPOIIa-DNA complex (PDB code: 2RGR) 14 were performed using PatchDock, 15 a molecular rigid-body docking algorithm based on shape complementarity principles. The 20 best ranking complexes, according to PatchDock scoring function, were visually analyzed and the complex displaying the highest number of molecular interactions was chosen and displayed.…”

“…15 PatchDock analysis returned 20 stereochemically feasible RSV-TOPOII complexes which were further analyzed in terms of the number of hydrogen bonds. The best complex resulting from this latter analysis is shown in Figure 1.…”

Geometric Analysis of Melamine Crystal: A Problematic Molecule Inducing Renal Failure in Melamine Intoxication

“…Biochemically, the melamine crystal is the compound between melamine and cyanuric acid. The standard docking technique on both molecules was performed via PatchDock, [5] and geometrical analysis of the output was further analyzed by Swiss-Pdb Viewer (GlaxoSmithKline R&D and the Swiss Institute of Bioinformatics). This technique is already described and proved for reliability in a previous published work.…”

Molecular Structure of Human Transferrin – Transferrin Receptor Complex

“…The human Tf and TfR were selected. Then a computational molecular technique, PatchDock [11], was used for modeling of the recombination. Briefly, PatchDock is a computational molecular technique for molecular docking based on shape complementarity principle [11].…”

“…Then a computational molecular technique, PatchDock [11], was used for modeling of the recombination. Briefly, PatchDock is a computational molecular technique for molecular docking based on shape complementarity principle [11]. The input is two molecules of any type: proteins, DNA, peptides, drugs [6].…”