Document Type
Thesis
Date of Award
12-31-1990
Degree Name
Master of Science in Engineering Science- (M.S.)
Department
Chemical Engineering, Chemistry and Environmental Science
First Advisor
Tamara M. Gund
Second Advisor
Carol A. Venanzi
Third Advisor
Barbara B. Kebbekus
Abstract
Thirty two anatoxin agonist analogues were investigated by means of computerassisted molecular modeling studies to delinate factors that may contribute to potency. The structures were generated from the fragment libraries from the SYBYL program, and minimized by the MM2 program. Then a systematic conformational search was done based on the global minimized structures to get bioactive conformations.
Ten agonists were further studied after the conformation optimization. The most potent agonists among these analogues, (+)-anatoxin-a (11), about 300 times as potent as carbamylcholine, severed as a template for the rest to examine the superimposability of the hydrogen bonding acceptor site and the cationic head. The electrostatic potentials (ESP) at Wan der Waals surfaces of the agonists were calculated and visualized by the ARCHEM program. The factors that seem important to the potencies are: (1) The global minimum structure; (2) The closeness of fit between the bioactive conformation and the template agonist (11); (3) The high potential region of the ESP about the cationic head; (4) The low potential region of the ESP about the hydrogen bonding acceptor; (5) The presence of the acetyl-like methyl group bearing the hydrogen bonding acceptor.
Recommended Citation
Yao, Qizhan, "Molecular modeling studies of anatoxin agonist analogues" (1990). Theses. 2680.
https://digitalcommons.njit.edu/theses/2680
