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Computing ionization states of proteins with a detailed charge model
Journal article   Peer reviewed

Computing ionization states of proteins with a detailed charge model

Jan Antosiewicz, James M. Briggs, Adrian H. Elcock, Michael K. Gilson and J. Andrew McCammon
Journal of computational chemistry, Vol.17(14), pp.1633-1644
11/15/1996
DOI: 10.1002/(SICI)1096-987X(19961115)17:14<1633::AID-JCC5>3.0.CO;2-M

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Abstract

A convenient computational approach for the calculation of the pKas of ionizable groups in a protein is described. The method uses detailed models of the charges in both the neutral and ionized form of each ionizable group. A full derivation of the theoretical framework is presented, as are details of its implementation in the UHBD program. Application to four proteins whose crystal structures are known shows that the detailed charge model improves agreement with experimentally determined pKas when a low protein dielectric constant is assumed, relative to the results with a simpler single-site ionization model. It is also found that use of the detailed charge model increases the sensitivity of the computed pKas to the details of proton placement. © 1996 by John Wiley & Sons, Inc.

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