Re-docking of available MPro co-crystal ligands by Maria Kadukova@MASIM SARS Cov2 event (Nov 2020)
Channel: GT-MASIM
Date: 2020-12-28

Presentation delivered by Maria Kadukova (PhD candidate@Nano-D, Inria Grenoble, France) during a series of talks organized in Nov 2020 by the French MASIM research group, dedicated to the structural bioinformatics aspects of SARS-CoV-2 research.

"Re-docking of the available MPro co-crystal ligands"
Abstract: Starting from 2013, our team has been developing knowledge-based protein-ligand scoring functions,namely Convex-PL, Convex-PL-R, and KORP-PL. We took the opportunity of assessing our methods on the recent Covid-19 structural data, and ran a series of re-docking experiments with the Mpro structures. The covalent nature of binding of the majority of its known co-crystal ligands made the docking process rather challenging.We have tried both covalent and non-covalent protocols. Covalent docking done with AutoDock Vina produced poses with rather low RMSDs if the covalent link was known. However, in a realistic scenario with unknown covalent links, docking with the search for the chemically possible links resulted in favoring unnatural binding poses. Non-covalent docking with our in-house version of AutoDock Vina and subsequent re-scoring with KORP-PL provided the 2.73 A median RMSD in cross-docking of 36 ligands with re-generated initial ligand structures and excluded native receptors. This was the most successful protocol among those we assessed and can be further used for the virtual screening or Mpro inhibitors. In this talk we would like to discuss our protocols and the problems we have encountered.
URL/DOI: https://team.inria.fr/nano-d/software/

MASIM is a research group within the French CNRS research network for bioinformatics (GdR BIM). Its goal is to promote collaborations and the dissemination of algorithmic methods for structural bioinformatics through an interdisciplinary dialogue involving, but not limited to, Biologists, Computer scientists, Chemists, Mathematicians and Physicists.