Dr. Chinmayee Choudhury is currently working as a DST-INSPIRE Faculty at All India Institute of Medical Sciences (AIIMS), Jodhpur since 2017. After obtaining a master’s degree in bioinformatics with a University gold medal, she received INSPIRE Fellowship from DST, India and pursued her doctoral degree in computational natural sciences from CSIR-IICT and IIIT, Hyderabad. She worked as a SERB-National Postdoctoral Fellow CSIR-IMTECH, Chandigarh for about a year after receiving the doctoral degree in 2015. Computer aided drug design, biomolecular modelling and cheminformatics are the major fields of her research. Her work is focused on discovery of novel chemotypes to specifically inhibit multi drug resistant strains of Mycobacterium tuberculosis aided by cell penetrating peptides as effective transporters.

Abstract OpenTox Asia 2019

Exploring multiple binding pockets of drug targets as a new strategy for Anti-TB inhibitor design

All biological functions are outcome of molecular interactions among biological macromolecules or with the metabolites in the cell. This knowledge is used to target essential proteins of pathogenic organisms in order to inhibit the physiological functioning of these proteins thereby killing the organism. Most often small molecules, which are substrate mimic of the protein (enzyme in this case), are used to competitively bind to the protein via specific interactions (which can be used to design a pharmacophore) in the binding pocket. However, in cases where the substrate is small in size and cannot offer specificity of binding to the protein, additional information on cofactor binding interactions may be utilized to design a molecule that can form interactions with both the substrate binding site and the cofactor binding site. It is also important to mention that since cofactors are common to both the host and the pathogen, their interactions alone cannot be used to design inhibitors as it may lead to off-target binding. Therefore, in this study, we have reported a unique approach to design a hybrid molecule that can form interactions with the substrate and the cofactor binding site. We have demonstrated the application of this method using a validated drug target (DapB) for Mycobacterium tuberculosis. Molecular dynamics approaches are used to build the hybrid pharmacophore models. Using a library of over 10 million compounds, these models are then validated for their ability to scan chemically diverse and druglike chemotypes, which may serve as starting points to design potential target-specific inhibitors for DapB.