The pKa Cooperative: A collaborative effort to advance structure-based calculations of pKa values and electrostatic effects in proteins
✍ Scribed by Jens E. Nielsen; M. R. Gunner; Bertrand García-Moreno E.
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 162 KB
- Volume
- 79
- Category
- Article
- ISSN
- 0887-3585
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
The p__K__~a~ Cooperative (http://www.pkacoop.org) was organized to advance development of accurate and useful computational methods for structure‐based calculation of p__K__~a~ values and electrostatic energies in proteins. The Cooperative brings together laboratories with expertise and interest in theoretical, computational, and experimental studies of protein electrostatics. To improve structure‐based energy calculations, it is necessary to better understand the physical character and molecular determinants of electrostatic effects. Thus, the Cooperative intends to foment experimental research into fundamental aspects of proteins that depend on electrostatic interactions. It will maintain a depository for experimental data useful for critical assessment of methods for structure‐based electrostatics calculations. To help guide the development of computational methods, the Cooperative will organize blind prediction exercises. As a first step, computational laboratories were invited to reproduce an unpublished set of experimental p__K__~a~ values of acidic and basic residues introduced in the interior of staphylococcal nuclease by site‐directed mutagenesis. The p__K__~a~ values of these groups are unique and challenging to simulate owing to the large magnitude of their shifts relative to normal p__K__~a~ values in water. Many computational methods were tested in this first Blind Prediction Challenge and critical assessment exercise. A workshop was organized in the Telluride Science Research Center to objectively assess the performance of many computational methods tested on this one extensive data set. This volume of Proteins: Structure, Function, and Bioinformatics introduces the p__K__~a~ Cooperative, presents reports submitted by participants in the Blind Prediction Challenge, and highlights some of the problems in structure‐based calculations identified during this exercise. Proteins 2011; © 2011 Wiley‐Liss, Inc.