Conformational analysis of glutathione molecular umbrella was performed with molecular dynamics simulated annealing and semi- empirical AMI methods. The results show that the difference of the lowest energy values in vacuum between exposed and shielded conformations is small (26.00 kj/mol). When solvent effect is included, the energy of the shielded conformation is highest and the exposed conformation lowest. The lowest energy of the shielded conformation is higher than the lowest energy of the exposed conformation by 89.24 kj/mol. This point accounts for why the exposed conformation of glutathione molecular umbrella exists in water. The influencing factors that glutathione molecular umbrella penetrates lipid bilayers with the shielded conformation were analyzed with VolSurf parameters. The results show that the major influencing factors are smaller amphiphilic moment and larger molecular rugosity of the shielded conformation, which are independent of definite hydrophobic regions of the conformation.

Key words: GLUTATHIONE, CONFORMATION, DRUGS DESIGN, HYDROPHOBILITY