MM3(96) parameterization for camptothecin analogs: An ab initio and molecular mechanics study |
| |
Authors: | Sean W. Carrigan Jenn-Huei Lii J. Phillip Bowen |
| |
Affiliation: | (1) Computational Center for Molecular Structure and Design, Department of Chemistry, University of Georgia, Athens, GA, 30602-2556, U.S.A. |
| |
Abstract: | Torsional parameters for MM3(96) were derived for the missing atom types present in thenatural product camptothecin (CPT). Potential energy curves were calculated via ab initiocalculations on representative compounds for dihedral angles containing these missingparameters. Gaussian 92 at the restricted Hartree–Fock level of theory using thestandard 6-31G** and 4-31G** basis sets, was used for all the quantum-mechanicscalculations. Missing MM3 torsional terms were obtained by optimizing the V1, V2 and V3parameters such that MM3 could reproduce the ab initio torsional profile. MM3 calculatedmolecular structures that compare well with the ab initio results. Using the newly developedparameters, conformational analyses and QSAR studies of camptothecin analogs wereundertaken. MM3 predicts two distinct boatlike conformations for the -hydroxy lactonemoiety. The low-energy lactone conformation predicted by MM3 is in general agreement withreported X-ray crystal structures of CPT iodoacetate and 7-ethyl-10-(4-piperidino)piperidinylcarbonyloxy CPT HCl as well as the ab initio structure of a CPT-like-hydroxy lactone. |
| |
Keywords: | Molecular mechanics MM3 Dihedral driver Camptothecin /content/kvr985kpk7g35ru6/xxlarge945.gif" alt=" agr" align=" BASELINE" BORDER=" 0" >-Hydroxy lactone |
本文献已被 SpringerLink 等数据库收录! |