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

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.

Molecular modeling software and methods for medicinal chemistry

“…Attempts to take into consideration the conformational energies during the fitting process have been made. 85,86 The more recent "ensemble distance geometry method77,87 will rapidly determine if any solutions exist without replacing a complete systematic search and, if so, provide a random sampling of solutions that indicates how uniquely determined the model is. Additional advantages of this approach are that it handles rings naturally without the ring closure difficulties encountered in dihedral search methods and that chirality can be allowed to vary for any stereo centers of unknown absolute configuration.…”

A Novel Transport Mechanism for MOMP in Chlamydophila pneumoniae and Its Putative Role in Immune-Therapy

“…Protomol generation and definition of the ligand binding groove was performed using a ligand directed method, which allows the docking of ligands into predefined sites as defined by occupancy of co-crystallised ligands. An overall energy minimisation of each MHC was performed using the Tripos force field [45] and employing a conjugate gradient algorithm [44] with a convergence criterion of 0.05 kcal/mol A −1 .…”

Recognition of ephedrine enantiomers by molecularly imprinted polymers designed using a computational approach

“…All of these structures were then charged with the Gasteiger-Huckel computational method, and refined by the molecular mechanics method (often called force field method), applying an energy minimization using the MAXIMIN2 command. 10 This command enables one to optimize the geometry and to minimize the strain energy of a given molecule. In the second step, the LEAPFROG algorithm was used to screen the library of functional monomers on their possible interactions with the template.…”