School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Proteins. 2011 Dec;79(12):3249-59. doi: 10.1002/prot.23194. Epub 2011 Oct 15.
The pK(a) Cooperative (http://www.pkacoop.org) was organized to advance development of accurate and useful computational methods for structure-based calculation of pK(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 As a first step, computational laboratories were invited to reproduce an unpublished set of experimental pK(a) values of acidic and basic residues introduced in the interior of staphylococcal nuclease by site-directed mutagenesis. The pK(a) values of these groups are unique and challenging to simulate owing to the large magnitude of their shifts relative to normal pK(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 pK(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.
PK(a) 协同组织（http://www.pkacoop.org）旨在促进开发准确有用的计算方法，以基于结构计算蛋白质中的 pK(a) 值和静电能。该协同组织汇集了在蛋白质静电理论、计算和实验研究方面具有专业知识和兴趣的实验室。为了改进基于结构的能量计算，有必要更好地理解静电效应的物理性质和分子决定因素。因此，该协同组织旨在推动对依赖静电相互作用的蛋白质基本方面的实验研究。它将维护一个实验数据存储库，这些数据对于评估基于结构的静电计算方法非常有用。为了帮助指导计算方法的发展，协同组织将组织盲测练习。作为第一步，邀请计算实验室重现一组未发表的由定点突变引入枯草溶菌素内部的酸性和碱性残基的实验 pK(a) 值。由于这些基团的变化幅度相对于水中的正常 pK(a) 值非常大，因此它们的 pK(a) 值是独特且难以模拟的。在这个第一个盲测挑战和关键评估练习中，测试了许多计算方法。在特柳赖德科学研究中心组织了一个研讨会，客观评估了在这个广泛数据集上测试的许多计算方法的性能。本期《蛋白质：结构、功能与生物信息学》介绍了 PK(a) 协同组织，介绍了盲测挑战参与者提交的报告，并强调了在该练习中发现的一些基于结构计算的问题。
