Screening And Modification Of The Hiv Protease Peptide Inhibitors And Structure-activity Relationship Study

As the theory and methods of computer-aided drug design become more powerful, studies on the interaction mechanism of biomolecules with lead compounds and the structural prediction of proteins have great theoretical and practical significance, and it could expedite the process of discovering new drugs. Around these hot topics, we perform theoretical studies on ligands with enzymes and receptors relating to vital diseases, and drug designing.This dissertation is composed of four chapters.Chapter 1: gives a brief introduction and proceedings of drug design.Chapter 2: investigates peptides in complex with the Human Immunodeficiency Virus protease found in the PDB bank, using flexible molecule alignment and molecular docking. Predicts the similarities between the inhibitors and Saquinavir. Finds those inhibitors have difference inhibiting abilities to HIV protease.The work has practical usage in new compound design.Chapter 3: studies the interacting mode of inhibitors with HIV protease by QSAR.The obtained molecular models predicts the biological activity index IC₅₀ of threecongeneric inhibitors. This QSAR model can be used for prediction.Chapter 4: selectes the AHPBA as the candidates for inhibitor design for Human Immunodeficiency Virus protease. The cleavable peptides are modified according to the "distorted key" theory, and the new inhibitors are formed. These conclusions and methods used in this design set a base for design of peptide inhibitors and nonpeptide inhibitors for the Human Immunodeficiency Virus protease.