Strategic approaches to drug design. I. An integrated software framework for molecular modelling

Abstract

An integrated molecular graphics and computational chemistry framework is described which has been designed primarily to handle small molecules of up to 300 atoms. The system provides a means of integrating software from any source into a single framework. It is split into two functional subsystems. The first subsystem, called COSMIC, runs on low-cost, serial-linked colour graphics terminals and allows the user to prepare and examine structural data and to submit them for extensive computational chemistry. Links also allow access to databases, other modelling systems and user-written modules. Much of the output from COSMIC cannot be examined with low level graphics. A second subsystem, called ASTRAL, has been developed for the high-resolution Evans & Sutherland PS300 colour graphics terminal and is designed to manipulate complex display structures. The COSMIC minimisers, geometry investigators, molecular orbital displays, electrostatic isopotential generators and various interfaces and utilities are described.

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents

“…The structures a1-a4 and b1-b4 were generated using SYBYL 29 Sybyl molecular modeling package running on a Linux operating system, and their energy were minimized using the Powell method with a convergent criterion provided by the Tripos force field 30 .…”

Structural requirements at the melatonin receptor

“…The molecular geometries of the melatonin analogues were optimised to give the minimum energy conformations using a combination of Newton-Raphson and Simplex methods found in the COSMIC molecular modelling package obtained from Smith Kline and French Ltd., Welwyn Garden City, U.K. (Vinter et al, 1987).…”

QSAR studies for the inhibition of the transmembrane carbonic anhydrase isozyme XIV with sulfonamides using PRECLAV software

“…Furthermore, the external validation of all the proposed models was performed by crossvalidation tests [34]. Also, due care is made to investigate the chance correlation [32][33][34].…”

“…The next step was the rigorous optimization of the geometry using the Mopac software [32,33] for quantum mechanics calculation using the keywords string "AM1 Pulay gnorm ¼ 0.01 shift ¼ 50 geo-ok camp-king mmok bonds vectors".The output file from Mopac was used as input file for PRECLAV program [27,28] using these data, PRECLAV program calculated for each molecule the values for almost 400 whole molecule descriptors, specific for the program in question. The statistic calculations, including the QSAR equations, have been performed using the PRECLAVE program and best set of descriptor chosen/calculated.…”