Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

pKa Shifts in Small Molecules and HIV Protease: Electrostatics and Conformation

Published

Author(s)

R Luo, M S. Head, J Moult, M K. Gilson

Abstract

The generalized Born [GB] approximation is a reasonable electrostatic model that is fast enough for use with extensive conformational sampling. This study combines the GB model with a torsion-space sampling method to compute pKa shifts for a series of dicarboxylic acids and amino acids, and for the active-site aspartyl dyad in HIV-1 protease. The calculations agree rather well with experiment for the small molecules. Conformational analysis shows salt-bridging for the zwitterionic amino acids but otherwise modest electrostatic effects upon mean chain-lengths. The calculations also show that through-space electrical fields alone cannot account completely for the observed pKa shifts. The calculations for HIV protease agree reasonably well with experiment, despite the complexity of the system. The present computational approach should be useful for a variety of other applications.
Citation
Journal of the American Chemical Society
Volume
120
Issue
24

Keywords

electrostatic, free energy, generalized born, HIV protease, salt bridge

Citation

Luo, R. , Head, M. , Moult, J. and Gilson, M. (1998), pK<sub>a</sub> Shifts in Small Molecules and HIV Protease: Electrostatics and Conformation, Journal of the American Chemical Society (Accessed April 22, 2024)
Created June 24, 1998, Updated February 17, 2017