A ?quasi-flexible? automatic docking processing for studying stereoselective recognition mechanisms. Part I. Protocol validation

The main purpose of this work is the development and validation of a general scheme based on a systematic and automatic “quasi-flexible” docking approach for studying stereoselective recognition mechanisms. To achieve our goals we explore the conformational and configurational space for small- or medium-size flexible molecules in a systematic way, seeking a method that is both reasonably accurate and relatively fast from the computational point of view. In particular, we have developed a general computational protocol for the global molecular interaction evaluation (“Glob-MolInE”) to efficiently explore the orientational and conformational space of flexible selectors and selectands used in modern chiral high-performance liquid chromatography (HPLC); the enantioselective binding of the selector (S)-N-(3,5-dinitrobenzoyl)-leucine- n-propylamide (S)-1 towards the selectand N-(2-naphthyl)-alanine methyl ester 2 has been studied; the global minimum obtained for the homochiral associate [S(1)/S(2)] (Pop. >99%) is very close (RMS≃0.20) to the crystallographically determined structure.