Release Time:2019-03-09  Hits:

Indexed by: Journal Article

Date of Publication: 2013-02-06

Journal: JOURNAL OF MOLECULAR STRUCTURE

Included Journals: EI、SCIE

Volume: 1033

Page Number: 227-235

ISSN: 0022-2860

Key Words: HIV-1 PR; Inhibitor; Resistance; Mutation; Molecular dynamics simulation

Abstract: Acquired immune deficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV), which is infecting more humans and is expanding faster in the world. The illness interferes with the immune system, making people with AIDS much more likely to get infections, including opportunistic infections and tumors that do not affect people with working immune systems. HIV-1 PR is one of the major targets of anti-AIDS drug discovery. It is, therefore, necessary to develop some inhibitors against HIV-1 PR. In this work, we executed molecular dynamics (MDs) simulation of HIV-1 PR with drugs darunavir (DRV), amprenavir (APV), nelfinavir (NFV), and examined the resistant mechanism of L101, G48V, 154V, and L90M mutations of this PR, aiming at designing promising drugs. The comparative analysis suggests that the existences of dodecahydroisoquinoline ring at P1' subsite, 4-aminophenylsulfonamide at P2' subsite, and bis-tetrahydrofuranylurethane at P2 subsite are helpful for maintaining the high affinity of the inhibitor for the protease and exhibiting high potency against multiple drug resistance (MDR) mutant protease. (C) 2012 Elsevier B.V. All rights reserved.