Date Approved
4-16-2024
Embargo Period
4-16-2024
Document Type
Thesis
Degree Name
Master of Science (M.S.) in Pharmaceutical Science
Department
Chemistry and Biochemistry
College
College of Science & Mathematics
Advisor
Chun Wu, Ph.D.
Committee Member 1
Zhihong Wang, Ph.D.
Committee Member 2
Zhiwei Liu, Ph.D.
Keywords
computer-aided drug design, viral evolution dynamics, molecular dynamics simulation, near-neutral balanced selectionist theory, anti-HER2 chimeric antigen receptor, HER-2 positive cancer treatment
Subject(s)
Drugs-- Design; Cancer--Treatment
Disciplines
Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences
Abstract
This study encompasses three significant chapters focusing on diverse yet interconnected aspects of pharmaceutical research. Chapter 1 delves into the complexities of drug development, emphasizing the challenges and the pressing need for advanced technologies to streamline the process. Computational methods like Computer-Aided Drug Design (CADD) extend their scope beyond small molecules, aiding in the design of intricate biomolecules vital for biomedical advancements, especially in immunotherapy. Chapter 2 introduces the Near-Neutral Balanced Selectionist Theory (NNBST) validated through analysis of Dengue virus evolution. The unique features observed align with NNBST, surpassing existing theories. This approach offers a deeper understanding of viral evolution dynamics, identifying conserved segments critical for vaccine development and shedding light on potential drug targets, amplifying the battle against Dengue. Finally, Chapter 3 focuses on molecular dynamics simulations of a novel anti-HER2 Chimeric Antigen Receptor (CAR) for HER2-positive cancer treatment. The proposed Binding Induced Domain Dynamics Switch (BIDDS) unveils a new signal transduction mechanism, revolutionizing the understanding of CAR activation. This breakthrough not only challenges existing models but also opens avenues for broader applications in receptor-based therapies. These chapters collectively represent a multidisciplinary approach merging computational techniques, evolutionary biology, and molecular dynamics simulations, promising significant contributions to drug development, viral evolution understanding, and therapeutic advancements in cancer treatment.
Recommended Citation
Hryb, Mariya, "To decipher genomic evolution of dengue virus and to probe the activation mechanism of a HER2 directed chimeric antigen receptor toward computer aided drug design (CADD)" (2024). Theses and Dissertations. 3202.
https://rdw.rowan.edu/etd/3202
