Date of Award
Master of Science in Engineering Science- (M.S.)
Chemical Engineering, Chemistry and Environmental Science
Tamara M. Gund
David S. Kristol
Conformational search and molecular mechanics calculations were combined to investigate the structural flexibility of isoquinolone, the anatoxin series, and the ferruginine series. Ring searching allow all rational conformations to be generated.
Isoquinolone shows conformational similarity to isoarecolone but is much less potent which suggests that the proximity of the methyl group beta to the carbonyl groups affects the bioactivity of isoquinolone. The very active agonist-anatoxin, without a similar conformation as isoarecolone, shared a similar electrostatic potential contour in the vicinity between the two atoms connected to the electro-positive nitrogen and hydrogen bonding site. These phenomena were not found in ferruginine which has a similar conformation to anatoxin but less potent. The comparison of the various series implied that the geometric position of the nitrogen is not essential, but that the electrostatic potential around the binding sites is important.
Two FORTRAN programs were implemented and adapted to aid the molec-ular modeling. FDRING made an improvement in the speed of ring perception. CAGEATOM suggests a faster method to represent the electrostatic potential distribution on van der Waals surface.
Shang, Wen-chung, "Molecular modeling in anatoxin and other semirigid agonists" (1989). Theses. 1937.