pKa Shifts in Small Molecules and HIV Protease: Electrostatics and Conformation
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- 作者：Rui Luo ; Martha S. Head ; John Moult ; and Michael K. Gilson
- 刊名：Journal of the American Chemical Society
- 出版年：1998
- 出版时间：June 24, 1998
- 年：1998
- 卷：120
- 期：24
- 页码：6138 - 6146
- 全文大小：132K
- 年卷期：v.120,no.24(June 24, 1998)
- ISSN：1520-5126
文摘
The generalized Born (GB) approximation is a reasonableelectrostatic model that is fast enoughfor use with extensive conformational sampling. This studycombines the GB model with a torsion-spacesampling method to compute pKa shifts for aseries of dicarboxylic acids and amino acids, and for theactive-site aspartyl dyad in HIV-1 protease. The calculations agree ratherwell with experiment for the small molecules.Conformational analysis shows salt-bridging for the zwitterionicamino acids but otherwise modest electrostaticeffects upon mean chain lengths. The calculations also show thatthrough-space electrical fields alone cannotaccount completely for the observed pKa shifts.The calculations for HIV protease agree reasonably wellwithexperiment, despite the complexity of the system. The presentcomputational approach should be useful fora variety of other applications.