title: Structural and dynamical aspects of HIV-1 protease and its role in drug resistance.
abstract: Acquired immunodeficiency syndrome (AIDS) caused by the retrovirus human immunodeficiency virus (HIV) has become a major epidemic afflicting mankind. The Joint United Nations Program on HIV/AIDS (UNAIDS) projection shows the existence of millions of AIDS patients at the end of 2012. All the Food and Drug Administration (FDA)-approved drugs are getting ineffective due to resistance offered by the mutation-prone HIV. Hence, there is an urgent need for developing new drugs with greater potential. HIV life cycle is controlled by the activities of its essential proteins like glycoproteins (gp41 and gp120), HIV reverse transcriptase (HIV-RT), HIV integrase (HIV-IN), and HIV-1 protease (HIV-pr). This chapter focuses on the protein HIV-pr, which is important for the cleavage of Gag and Gag-Pol polyproteins to form mature, structural, and functional virions. The conformation and dynamics of the protein HIV-pr play a pivotal role in ligand binding and the catalytic process, which is affected by the rapid point mutations and various physiological parameters. The effect of the mutations and the varied simulation protocols on conformational dynamics and drug resistance of HIV-pr is discussed.
authors: Department of Chemistry, Gottwald Center for the Sciences, University of Richmond, Richmond, Virginia, USA. Electronic address: brmeher@gmail.com.
authors: Biswa Ranjan
authors: BR
authors: Meher
authors: Seema
authors: S
authors: Patel
mesh_terms: D000595:Amino Acid Sequence; D004351:Drug Resistance; D054303:HIV Reverse Transcriptase; D015497:HIV-1; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation
chemical_list: D054303:HIV Reverse Transcriptase
keywords: Drug resistance; Force field; HIV-1 protease; Molecular dynamics simulation; Mutation; Polarization; Protein conformation