Predicting protein pKa by environment similarity
- 14 January 2009
- journal article
- research article
- Published by Wiley in Proteins: Structure, Function, and Bioinformatics
- Vol. 76 (2), 484-495
- https://doi.org/10.1002/prot.22363
Abstract
A statistical method to predict protein pKa has been developed by using the 3D structure of a protein and a database of 434 experimental protein pKa values. Each pKa in the database is associated with a fingerprint that describes the chemical environment around an ionizable residue. A computational tool, MoKaBio, has been developed to identify automatically ionizable residues in a protein, generate fingerprints that describe the chemical environment around such residues, and predict pKa from the experimental pKa values in the database by using a similarity metric. The method, which retrieved the pKa of 429 of the 434 ionizable sites in the database correctly, was crossvalidated by leave-one-out and yielded root mean square error (RMSE) = 0.95, a result that is superior to that obtained by using the Null Model (RMSE 1.07) and other well-established protein pKa prediction tools. This novel approach is suitable to rationalize protein pKa by comparing the region around the ionizable site with similar regions whose ionizable site pKa is known. The pKa of residues that have a unique environment not represented in the training set cannot be predicted accurately, however, the method offers the advantage of being trainable to increase its predictive power. Proteins 2009.Keywords
This publication has 58 references indexed in Scilit:
- Prediction of Protein Solubility from Calculation of Transfer Free EnergyBiophysical Journal, 2008
- Analysis of Site-Specific Histidine Protonation in Human Prolactin,Biochemistry, 2008
- pK values of the ionizable groups of proteinsProtein Science, 2006
- Charge–Charge Interactions are Key Determinants of the pK Values of Ionizable Groups in Ribonuclease Sa (pI=3.5) and a Basic Variant (pI=10.2)Journal of Molecular Biology, 2003
- Calculated Protein and Proton Motions Coupled to Electron Transfer: Electron Transfer from QA- to QB in Bacterial Photosynthetic Reaction CentersBiochemistry, 1999
- Modeling of protein conformational fluctuations in pKa predictionsJournal of Molecular Biology, 1997
- Electrostatics and diffusion of molecules in solution: simulations with the University of Houston Brownian Dynamics programComputer Physics Communications, 1995
- pKA Values of Carboxyl Groups in the Native and Denatured States of Barnase: The pKA Values of the Denatured State Are on Average 0.4 Units Lower Than Those of Model CompoundsBiochemistry, 1995
- The Reversible Transformation of β-Lactoglobulin at pH 7.51Journal of the American Chemical Society, 1959
- Theory of Protein Titration Curves. I. General Equations for Impenetrable SpheresJournal of the American Chemical Society, 1957