Hydrophobic sliding: a possible mechanism for drug resistance in human immunodeficiency virus type 1 protease
Name:
Publisher version
View Source
Access full-text PDFOpen Access
View Source
Check access options
Check access options
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2007-02-13Keywords
Amino AcidsDrug Resistance, Viral
HIV Protease
HIV Protease Inhibitors
Hydrogen Bonding
Hydrophobicity
Mutation
Protein Conformation
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Hydrophobic residues outside the active site of HIV-1 protease frequently mutate in patients undergoing protease inhibitor therapy; however, the mechanism by which these mutations confer drug resistance is not understood. From analysis of molecular dynamics simulations, 19 core hydrophobic residues appear to facilitate the conformational changes that occur in HIV-1 protease. The hydrophobic core residues slide by each other, exchanging one hydrophobic van der Waal contact for another, with little energy penalty, while maintaining many structurally important hydrogen bonds. Such hydrophobic sliding may represent a general mechanism by which proteins undergo conformational changes. Mutation of these residues in HIV-1 protease would alter the packing of the hydrophobic core, affecting the conformational flexibility of the protease. Therefore these residues impact the dynamic balance between processing substrates and binding inhibitors, and thus contribute to drug resistance.Source
Structure. 2007 Feb;15(2):225-33. Link to article on publisher's site
DOI
10.1016/j.str.2007.01.006Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38492PubMed ID
17292840Related Resources
ae974a485f413a2113503eed53cd6c53
10.1016/j.str.2007.01.006