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Blind, one‐eyed, or eagle‐eyed? p K a calculations during blind predictions with staphylococcal nuclease
Author(s) -
Czodrowski Paul
Publication year - 2011
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.23110
Subject(s) - root mean square , protonation , binary number , mutant , chemistry , computer science , mathematics , physics , combinatorics , algorithm , biochemistry , gene , ion , quantum mechanics , arithmetic , organic chemistry
Abstract In the current contribution, the performance of Poisson–Boltzmann‐based p K a calculations of SNase mutants as part of a blind prediction exercise facilitated by the p K a cooperative (“p K a _coop”) is described. A one parameter setting (“quick&dirty” approach) is used to provide an industry perspective where strong time constraints are frequently encountered. On the one hand, results are analyzed in terms of root mean square deviation performance. Furthermore, the p K a calculations are assessed for their ability to properly assign protonation state. For this purpose, a new measure called BIPS (binary protonation state at physiological pH) is introduced. Significant differences were found with both comparison measures based on the class of residues examined. In addition, the performance of PROPKA3 as well as the NULL model is examined on the same data set. Finally, p K a calculations on SNase mutants with available structural information have been performed and provide support for our calculation methods. The performance on this subset is better than on the p K a cooperative mutation data. In the p K a _coop data, no structural information on the generated mutants is available. This suggests the occurrence of a substantial structural rearrangement on the insertion of additional charged groups into SNase, which leads to improved prediction quality. Proteins 2011;. © 2011 Wiley‐Liss, Inc.