FIRST PRINCIPLES STUDIES ON STRUCTURE-CARCINOGENICITY RELATION
Date
2023-11-22
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Thesis
Degree Level
Doctoral
Abstract
The question behind all works presented in this thesis is “why do similarly structured molecules exhibit distinct carcinogenic behaviors?” Answering this question is important to not only the fields of Pharmacology and Toxicology but also the development of drug design and testing. Our goal is to explain such a macroscopic phenomenon with atomic-level physico-chemical properties and ultimately develop a theoretical model which is capable of describing the corresponding structure-carcinogenicity relationships. General metabolism pathways, specific mechanisms of bio-chemical transformation as well as relevant background knowledge for ligand-protein interaction are introduced in the first chapter. Three theoretical tools are employed for probing the critical changes due to subtle deviations of molecular structures. Specifically, Density Functional Theory (DFT) for calculating the electron density distribution and related electric properties such as dipole moments and localized electrophilicity. Meanwhile, Molecular Dynamic (MD) simulations and Bio-molecular Docking are applied for investigating and visualizing molecular interactions which emphasize more on the influence of steric effects. Theoretical studies on the ligand-protein binding orientation, probability and equilibrium binding positions were carried out and presented in Chapter 3, 4 and 5, respectively.
Description
Keywords
structure-carcinogenicity, structure-activity, toxicity, molecular dynamics, density functional theory, simulation
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Physics and Engineering Physics
Program
Physics