OVID and SUPER: two overlap programs for drug design.
Two programs, OVID and SUPER, for exploring the similarity of molecules with respect to their action at a receptor are described. OVID accepts two molecules as input and optimizes the three-dimensional overlap of specified atoms in one molecule with specified atoms in the second molecule. The result is expressed as a percent of the theoretical maximum. OVID gives a quantitative measure of the extent of a guessed correspondence between two molecules based on volume overlap of selected atoms. The Achilles' heel of OVID is that the correspondence between the two molecules has to be guessed. We realized that it would be better to systematically examine all possible correspondences of two structures to minimize the chance of overlooking a superior correspondence. We created SUPER to satisfy this need. SUPER accepts two molecules as input and finds the top twenty correspondences of their surfaces and charge distributions, giving a quantitative measure of the extent of each correspondence. An instructive example of the application of OVID and SUPER to the design of leukotriene D4 receptor antagonists is described. SUPER appears to be a practical brain-storming tool for the medicinal chemist trying to understand how molecules whose structures may not resemble one another in an obvious way can bind to the same site.
Hermann
R B
RB
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Herron
D K
DK
D000098:Acetophenones / Q000737:chemistry*; D003198:Computer Simulation; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D011971:Receptors, Immunologic / Q000378:metabolism; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D012984:Software; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry*
D000098:Acetophenones; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; D013777:Tetrazoles; C044660:LY 171883; C058564:5-(4-(3,4-dichloro-2-propylphenoxy)butyl)-1H-tetrazole