Maria Beihaghi1,2,*,# , Houman Tehrani 3,# , Nazanin Akbari4, Mohamad Reza Beihaghi5, and Reza Sahebi6
1 Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran 2 School of Science and Technology, The University of Georgia, Tbilisi, Georgia 3 Department of Paediatric, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran 4 Department of Biology, Faculty of Sciences, Shahid Beheshti University, Tehran, Iran 5 Department of Psychology, Sheffield Hallam University, Sheffield, England 6 Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran # Maria Beihaghi and Houman Tehrani contributed equally to this study. * Corresponding author: Maria Beihaghi, Department of Biology, Kavian Institute of Higher Education, Mashhad, Iran; School of Science and Technology, The University of Georgia, Tbilisi, Georgia. Email: m.beyhaghi@um.ac.ir
Abstract:
Introduction: This research was conducted to investigate the molecular interaction of HIV protease inhibitor drugs using molecular docking. HIV protease is responsible for processing gag and gag-polyproteins during virion maturation. The activity of this enzyme is essential against viral infections and has beneficial therapeutic effects on HIV treatment. Materials and Methods: To meet the aim of the study, indinavir and ritonavir were selected as HIV Protease inhibitor drugs. The necessary information on molecular docking was collected through information servers, such as Drug bank and Program database (PDB). Then, molecular docking was performed using Molegro virtual docker software. In order to check the stability of the resulting complex structure and its cellular penetration, a molecular dynamics simulation was run for 50 nanoseconds using GROMACS2019.6 package and Amber99SB force force field. During the molecular dynamics simulation, root mean square deviations (RMSD), root mean square fluctuations (RMSF), the radius of gyration (RG), hydrogen bonds, and distance between ligands and complex were investigated. Results: The obtained results indicated that the RMSD of the complex of the ligands and HIV protease at the end of 50 nanoseconds had a linear slope. Hydrogen bonds decreased at beginning of simulation but they increase at the end of simulation However RG was decreased at the end of the simulation Also the RMSF was decreased at the end of simulation rather than beginning of simulation, So all the obtained results showing the stability and strength of the structure. Conclusion: Molecular docking method can indicate the relationship between structure-activity and the effectiveness of ligands on HIV protease based on the level of interaction between the ligands and the receptors.
1.Introduction:
Acquired Immune Deficiency Syndrome (AIDS) is a type of disease that occurs when the immunodeficiency virus severely attacks the immune system. The disease caused by the HIV virus has three main stages. In the first stage (acute infection), the person may be experiencing a short influenza-like illness, which is not the same in all people. For this reason, the disease usually follows for an extended period without any symptoms, called the latent period of the disease1. The more the disease progresses, the more weakness is found in the body’s immune system leading to infections, opportunistic cancers, and tumors although it is usually ineffective in people whose immune system is functioning well2. Finally, the disease will enter the third stage of AIDS when CD4 T cell count should be less than 200 cells per microliter. HIV is a virus from a group of retroviruses that attacks the body’s immune system cells3. This virus was discovered by Frenchman Luc Montagnier and American Robert Galloway4. Indinavir is taken orally and its consumption with fatty foods reduces its bioavailability and maximum blood concentration, but when consumed with low-fat food, food has no effect on drug absorption.
