PMID: 11340653May 8, 2001Paper

Molecular dynamics studies on HIV-1 protease drug resistance and folding pathways

Proteins
F CecconiA Maritan

Abstract

Drug resistance to HIV-1 protease involves the accumulation of multiple mutations in the protein. We investigate the role of these mutations by using molecular dynamics simulations that exploit the influence of the native-state topology in the folding process. Our calculations show that sites contributing to phenotypic resistance of FDA-approved drugs are among the most sensitive positions for the stability of partially folded states and should play a relevant role in the folding process. Furthermore, associations between amino acid sites mutating under drug treatment are shown to be statistically correlated. The striking correlation between clinical data and our calculations suggest a novel approach to the design of drugs tailored to bind regions crucial not only for protein function, but for folding as well.

Citations

Jul 27, 2002·Protein Science : a Publication of the Protein Society·Cristian MichelettiAmos Maritan
Oct 23, 2010·PloS One·Massimiliano BonomiMichele Parrinello
Oct 30, 2007·Biophysical Journal·Carlo GuardianiRoberto Livi
Jun 9, 2004·Journal of Molecular Biology·Yaakov LevyPeter G Wolynes
May 2, 2006·Biophysical Journal·Fabio CecconiRoberto Livi
Apr 23, 2004·Proteins·Raffaella BurioniAngelo Vulpiani
Oct 1, 2005·Protein Science : a Publication of the Protein Society·Ricardo A BrogliaFabio Simona
Feb 14, 2007·Proteins·R A BrogliaV Perelli
Jun 19, 2007·Biophysical Journal·Massimiliano BonomiMichele Parrinello
Dec 24, 2002·Biophysical Journal·Giovanni SettanniAmos Maritan
Oct 19, 2001·Biophysical Journal·G SettanniA Maritan

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