This industry talk will be taking place on 26 April 2023 at 3pm (UK time).

Registration: free, link here (deadline 25 April 2023)

Title: Introduction to Site Identification by Ligand Competitive Saturation (SILCS) and its Application in Drug Design and Development.

Speaker: Alexander D. MacKerell, Jr. - Department of Pharmaceutical Sciences, School of Pharmacy University of Maryland USA and SilcsBio LLC

Abstract: SILCS involves generating a pre-computed ensemble of 1) the distribution of solutes and water in the full 3D space of proteins or RNA as well as 2) the conformations of the macromolecule using combined oscillating excess chemical potential Grand-Canonical Monte Carlo/Molecular Dynamics simulations. From the precomputed ensemble 3D “FragMaps” are produced that represent functional group free energies relative to aqueous solution in the full 3D space of the macromolecular system.  The free energies include contributions on macromolecular flexibility, desolvation of the functional groups and the macromolecule and functional group-macromolecular interactions.  Once precomputed the SILCS FragMaps may be used for a variety of free energy related calculations in a highly computationally accessible manner.  These include binding affinities of fragments and drug-like molecules, generation of pharmacophores, and lead compound optimization. In addition, FragMaps may be utilized for calculation of protein-protein interactions, glycan-protein interactions, and the full distributions of ligands in the 3D space of macromolecules for use in allosteric binding site identification, fragment-based drug design, and the rational design of excipients for biologics drugs formulation.  In addition, the SILCS methodology may be applied to membranes allowing for investigations of the partitioning of molecules in interfacial systems and prediction of permeabilities in conjunction with artificial intelligence.  An introduction to the SILCS technology and details of various applications will be presented.