Allosteric Drug Design

The Computational Approach to Allosteric Drug Discovery

Allosteric drug design targeting DNMT1 Protein-Protein Interactions (PPIs) combining both biophysics and bioinformatics methods.

A mini review about molecular traits and personal comments on drug development for SARS-CoV-2

Highlights in the publication include 1)Dynamics and allosteric potentials of the RFTS domain are proposed. 2)Hinge sites located at the RFTS-CD interface are key regulators for inter-domain interactions. 3)Network analysis reveals local allosteric networks and inter-domain communication pathways in DNMT1. 4)A potential allosteric site at the TRD interface for DNMT1 is identified.

Computational tools now provide reliable assessments of hot spots and pockets found in PPIs, proving reasonable starting points for epigenetic drug design. In this chapter, a hybrid approach, comprising protein structure network, elastic network model, perturbation response scanning and sequence evolution analysis, was proposed for the systematic study of intrinsic dynamics, allostery regulation principle, allosteric sites and pockets. By applied this integrating approach to DNMT1 and DNMT3A, the roles of protein-protein and domain-domain interactions in allosteric drug design were highlighted.