The New Jersey Institute of Technology's
Electronic Theses & Dissertations Project

Title:	Computer assisted molecular modeling of thymidine nucleoside analog inhibitors of HIV-1 reverse transcriptase
Author:	Fisher, Mark A.
View Online:	njit-etd1993-081 (xi, 69 pages ~ 3.8 MB pdf)
Department:	Biomedical Engineering Committee
Degree:	Master of Science
Program:	Biomedical Engineering
Document Type:	Thesis
Advisory Committee:	Kristol, David S. (Committee co-chair) Yadav, Janardan (Committee co-chair) Modak, Mukund J. (Committee member)
Date:	1993-10
Keywords:	Reverse transcriptase Nucleosides HIV (Viruses) Molecular structure -- Computer simulation Biomolecules -- Computer simulation DNA polymerases
Availability:	Unrestricted
Abstract:	An active analog approach to receptor mapping was used to identify the three dimensional structural characteristics associated with a series of thymidine nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) that may be essential for their activity. Atomic substitutions at the 5 and 3' positions of nucleoside analogs confer global structural and electrostatic changes that result in either increased or diminished inhibitory activity. From a structural perspective, the activity differences can be attributed to the presentation of select atoms in three dimensional motifs that are common to all active compounds and absent or distorted in inactive/poorly active compounds. The identification of these characteristics will complement more direct studies of the RT structure by providing a specific three dimensional orientation for substrate and inhibitor molecules at their receptor site. They can also serve as a three dimensional template for the screening of potentially active compounds; thus, aiding in the development and identification of new, more potent and selective inhibitor molecules. The characteristics identified are common to 15 thymidine nucleoside analog inhibitors of RT and have allowed the inference of a three dimensional map of the HIV-1 RT receptor site.