Computational Biochemistry Home
Research Interest

Understanding the functioning of the peptide bond and phosphoester cleaving enzymes and the designing of their synthetic analogues: The primary goal of this project is to derive guiding principles of peptide and phosphoester hydrolysis from theoretical calculations and apply them in close collaboration with experimentalists for the development of efficient bio-inspired synthetic metallohydrolases. The selective hydrolysis of peptide and phosphoester bonds of proteins and DNA, respectively, plays critical roles in a wide range of biological, biotechnological and industrial applications. In biology, these processes are implicated in functional and regulatory roles in the control of the cell cycle, cell death, DNA repair and energy metabolism. In biotechnology, they are involved in protein engineering proteomics, protein footprinting, genomics, therapeutics and bioremediation of pesticides and nerve agents. Furthermore, more than 60% of all industrial enzymes are hydrolases that are used in a wide range of industries such as textile, food, leather, pharmaceutical, paper and ethanol production. The structural and mechanistic information derived from these studies has also been utilized to develop their “designer” forms with distinct substrate specificities and drug molecules in the form of inhibitors and activators.

Elucidating the aggregation mechanisms of disease related biomolecules and designing of their inhibitors: This project concerns investigating the mechanisms of aggregation of biomolecules such as amyloid beta (Aβ) peptides and insulin and the designing of small molecules for inhibition of this process. The aggregation of biomolecules has been implicated in a large number of neurological disorders such as Alzheimer’s disease, Parkinson’s disease and Creutzfeldt-Jakob disease.  


Novel biomaterials design based on protein aggregates: The goal of this project is to derive a fundamental understanding of the sequence-structure-material properties relationship for fibrillogenic proteins and apply it for the development of novel biomaterials for bio-nano-med applications. These materials are formed by natural amyloidogenic peptides such as amyloid beta (Aβ) and insulin and possess some remarkable properties such as elasticity, sturdiness, resistance and self-healing.  


Designing novel antimicrobial compounds: This project involves the development and mechanistic studies of the next generation of antimicrobial peptides (AMPs) such as ATCUN-sh-Buforin. The emergence of antibiotic resistant strains of bacteria has resulted in the need to develop more potent antimicrobials that target microorganisms in a novel manner.  Naturally occurring AMPs show great potential for drug development because of their broad activity and unique mechanism of action.


Studying protein-protein interactions in neuronal formation: This project concerns the development and implementation of a hybrid approach involving in-vivo and in-silico techniques to investigate interactions between three critical proteins (Cdc42, WASp and Par6). These proteins have been implicated to play critical roles in neuronal development. A deeper understanding of these interactions will help us understand the molecular mechanisms of the pathogenesis of deadly diseases such as the brain tumor.


All these projects combine fundamental principles of chemistry with state-of-the-art applications such as the design of small drug molecules, designer forms of enzymes, synthetic analogues of metalloenzymes, biomaterials and antimicrobial compounds. We have been employing a plethora of innovative theoretical and computational chemistry techniques involving molecular dynamics (MD), quantum mechanics (QM), hybrid quantum mechanics/molecular mechanics (QM/MM), nuclear spin relaxation, molecular docking, agent based modeling and in-silico screening to comprehend these processes at the atomic level.