Three‐Dimensional Quantitative Structure‐Activity Relationships. 2. Conformational Mimicry and Topographical Similarity of Flexible Molecules

Abstract

Abstract A molecular mechanics program (Maximin) is described with emphasis on its distinctive features. With Maximin, energy can be minimized while maintaining specified geometric relationships within and/or among given sets of atoms. Additionally, two alternative methods for conformational comparisons are supported: a set of flexible molecules can be mapped onto a rigid reference structure, or treating all molecules as flexible entities, one can minimize the conformational variance of the set. The latter method is described here for the first time. Calculations of methotrexate‐dihydrofolate reductase interaction energy, and the analysis of a series of structurally diverse inhibitors of angiotensin converting enzyme are reported. Algorithmic description of the original features of Maximin is also provided.