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Doctor of Philosophy (PHD)
Chemistry (Arts and Sciences)
Date of Defense
First Committee Member
Second Committee Member
Thomas K. Harris
Third Committee Member
James N. Wilson
Fourth Committee Member
In this thesis, innovative theoretical and computational techniques including quantum mechanics (QM), hybrid quantum mechanics/molecular mechanics (QM/MM ONIOM), molecular dynamics (MD) simulations and molecular docking methods are employed to derive the structural and mechanistic information of functioning of proteolytic enzymes (aspartyl proteases and metallopeptidases) and aggregation mechanisms of amyloid beta (Aβ) peptide associated with Alzheimer’s disease (AD). In particular, the enzyme-substrate interactions and substrate hydrolysis mechanisms utilized by these proteolytic enzymes and their synthetic analogues are studied at the atomic level. An alternative strategy to design novel inhibitors for aspartyl proteases and to inhibit the aggregation of the Aβ peptide has also been explored. In addition, the role of the Aβ peptide in the oxidative stress mechanism has been investigated. These studies elucidate the mechanisms of peptide hydrolysis catalyzed by proteases and their synthetic analogues and suggest alternative strategies for the design of novel inhibitors. The results gleaned from these studies will advance scientific efforts to develop therapeutic interventions for the treatment of AD.
Aspartyl protease; Peptidase; Amyloid beta; Computational; Molecular dynamics; QM/MM
Barman, Arghya, "Mechanistic and Structural Studies of Proteases, Peptidases and Amyloid Beta Peptide: An Integrated Computational Approach" (2012). Open Access Dissertations. 795.