Abstract

IN SILICO MOLECULAR DOCKING STUDIES ON NOVEL PEPTIDE ANALOGUES AS POTENT HIV PROTEASE INHIBITORS AGAINST HIV

Pavan P.*, Suvarnalakshmi G., Habeela Jainab N., Sriharsha S. N., Sheshagiri R. Dixit and Richa Shetty

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Abstract

AIDS is a sexually transmitted disease that is caused by the HIV. The HIV-1 protease enzyme plays a very important role in the life cycle of HIV. By understanding the importance of the HIV-1 protease enzyme, studies related to the inhibition of protease enzyme has increased in treatment of the AIDS. Structure-based drug design by use of structural biology remains one of the most logical and aesthetically pleasing approaches in drug discover paradigms. Managing AIDS, is the most challenging problems in the 21st century. The concept of structurebased drug discovery combines information from several fields, X-ray crystallography and/or NMR, molecular modeling, synthetic organic chemistry, qualitative structure-activity relationships (QSAR), and biological evaluation. We examined the protease inhibitory activities of the peptide compounds containing heteroatoms. The mechanism of inhibition can be related to the catalytic mechanism of protease action or include mechanism unrelated stearic blockage of the active site or its neighborhood. Protease inhibitor drugs block the action of protease enzymes. This prevents protease enzymes from doing their part in allowing HIV to multiply, interrupting the HIV life cycle as a result controls the disease. In the current study we planned to design some novel N-substituted pentacycloundecane peptide derivatives and identify the compounds with effective binding action on selected target HIV protease by using molecular docking studies. In silico docking studies were carried out using BIOVIA Discovery Studio. The results showed that most of the chemical compounds binds effectively with HIV protease enzyme. Among the docked compounds, the compound 45, compound 9, compound 37, compound13, compound 41, and compound 6 shows higher –cdocker energy and -cdocker interaction energy than the standard drug whereas the other analogues showed comparatively lower scores.

Keywords: HIV, HIV protease enzyme, peptide analogues, molecular docking.