Docking and Molecular Dynamics Calculations of Some Previously Studied and newly Designed Ligands to Catalytic Core Domain of HIV-1 Integrase and an Investigation to Effects of Conformational Changes of Protein on Docking Results

Abstract

Nowadays, AIDS still remains as a worldwide pandemic and continues to cause many deaths which arise from HIV-1 virus. For nearly 35 years, drugs that target various steps of virus life cycle have been developed. HIV-1 integrase constitutes one of these steps which is essential for virus life cycle. Computer-aided drug design is being used in many drug development and drug improvement studies as also used in development of the first HIV-1 integrase inhibitor Raltegravir. In this study, 3 ligands which are already used as HIV-1 integrase inhibitors and 4 newly designed ligands were docked to catalytic core domain of HIV-1 integrase. Each ligand docked to three different conformations of protein. Prepared complexes (21 items) were carried out by 50 ns MD simulations and results were analyzed. Finally, the binding free energies of ligands were calculated. It was determined that designed ligands L01 and L03 gave favorable results. The questions about the ligands which have low docking scores in a conformation of protein could give better scores in another conformation of protein and if the MD simulations carry the different oriented and different localized ligands in same position at the end of simulation were answered.

A molecular docking study of potential inhibitors and repurposed drugs against SARS-CoV-2 main protease enzyme

“…Ligand library was generated as follows; previously used for both HIV-1 IN inhibition and 3-Hydroxy-3-methyl-glutaryl-CoA Reductase Enzyme (HMGR) (10 ligands) [ [19] , [20] , [21] ] inhibition, 104 ligands used for HMGR (ligands coded as HMXXX) [ 21 ] enzyme inhibition, 1637 ligands used for EBV EBNA1-DNA binding blockers (ligands coded as EBXXX, EYXX, and EZXXXX) [ 22 ], and 426 ligands used as HIV-1 RT-IN dual inhibitors (ligands coded as HBXX) [ 23 ]. Designing procedure of these ligands have been described in the related publications.…”

Molecular Docking Study of Four Chromene Derivatives as Novel HIV-1 Integrase Inhibitors

“…The HIV replication cycle involves the integration of viral DNA into the host chromosome, which is an essential process conducted by the viral integrase (IN) protein. This protein, together with reverse transcriptase and protease, is one of three enzymes encoded by HIV (2). The current antiviral therapy for treatment of AIDS includes a combination therapy with reverse transcriptase and protease inhibitors with a potential therapeutic capability (3).…”