Protein electrostatics and pKa blind predictions; contribution from empirical predictions of internal ionizable residues

✍ Scribed by Mats H. M. Olsson

• Book ID: 105358292
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 899 KB
• Volume: 79
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/prot.23113

✦ Synopsis

Abstract

In this study, we validate and probe the description of electrostatic interactions within proteins by predicting and comparing p__K__~a~ values of ionizable groups in a series of mutated staphylococcal nuclease variants with experiments. This set of p__K__~a~ values is found to be the most challenging p__K__~a~ data to date, because ionizable residues have been introduced in hydrophobic patches in the protein interior and are therefore significantly shifted from their reference solvated values. We find that using PROPKA2 (Li et al., Proteins 2005;61:704–721) results in an rmsd value close to 2 for true blind predictions (1.6 if we reassign the tightly coupled Asp19/21 pair) and close to 1 for postpredictions with the newly developed PROPKA3 (Olsson et al., J. Chem. Theor. Comp. 2011;7:525–537). We also use the performance of the Null‐model, predictions made with the reference value only, to provide a better description of the expected errors in p__K__~a~ predictions and to compare submissions made using different subsets of the p__K__~a~ data more consistently. Proteins 2011; © 2011 Wiley‐Liss, Inc.