THEORETICAL CALCULATIONS ON CYCLOHEXAGLYCINE AND 3-DIMENSIONAL DERIVATIVES - CONFORMATIONAL-ANALYSIS AND CALCULATIONS OF HOST-GUEST PROPERTIES OF PEPTIDES

Molecular modelling studies combining computer graphics, molecular mec hanics and molecular dynamics calculations are reported for some pepti de systems. Conformation analyses have been carried out for cyclohexag lycine and two basket-like three-dimensional derivatives, and some pre liminary calculations have been carried out to investigate their prope rties as binding agents with another peptide molecule N-acetyl-L-alani ne (N-Ac-L-Ala). After an exhaustive conformational search on the cycl ohexaglycine, several features involved in the recognition properties displayed by these compounds were analysed: the conformational prefere nces of the free and complexed receptors, binding affinity, nature and orientation of binding sites and the macro(poly)cyclic effect. There are considerable changes in the cyclohexaglycine conformation when it is either inserted in a three-dimensional structure or when it interac ts with other peptide molecules, thus simulating protein structures. T he dual features of the flexibility and/or the rigidity of the ligands must be taken into account in order to gain an understanding of molec ular recognition. In addition to hydrogen bonding effects, we found th at electrostatic and hydrophobic interactions play an important role i n the molecular recognition of neutral molecules.