Publication Date



Open access

Embargo Period


Degree Type


Degree Name

Doctor of Philosophy (PHD)


Chemistry (Arts and Sciences)

Date of Defense


First Committee Member

Rajeev Prabhakar

Second Committee Member

Roger LeBlanc

Third Committee Member

James N. Wilson

Fourth Committee Member

Amjad Farooq


In this thesis, we have focused on the following two projects: (1) mechanisms of peptide hydrolysis, and (2) aggregation of biomolecules. A plethora of theoretical and computational techniques; quantum mechanics, molecular dynamics, and molecular docking have been employed to accomplish the goals of these projects. The selective hydrolytic cleavage of the extremely stable peptide bond (-(O=)C-NH-) of peptides and proteins by enzymes and their analogues is required in a wide range of biological, biotechnological and industrial applications. In the first project, we have elucidated the mechanisms of peptide hydrolysis by non-metallic (beta secretase (BACE)) and metallic (insulin degrading enzyme (IDE) and neprilysin (NEP)) enzymes and the synthetic analogues of metallo-enzymes. In addition, mechanisms of activation of IDE through small molecules and alteration in substrate specificity of NEP have been investigated. The aggregation of biomolecules has been implicated in a large number of neurological disorders. In the second project, the aggregation mechanisms of insulin and Alzheimer`s amyloid beta (Aβ) peptide have been studied. The interactions between the Aβ peptide and Ru complexes have also been explored. In another project, we have investigated the mechanism oxygen activation by Cu-containing amine oxidases (CAOs) by computing kinetic isotope effect (KIEs).


computational; biomolecules; theoretical chemistry; aggregation; hydrolysis