Gordon John C, Myers Jonathan B, Folta Timothy, Shoja Valia, Heath Lenwood S, Onufriev Alexey
Department of Computer Science, Virginia Tech Blacksburg, VA 24061, USA.
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W368-71. doi: 10.1093/nar/gki464.
The structure and function of macromolecules depend critically on the ionization (protonation) states of their acidic and basic groups. A number of existing practical methods predict protonation equilibrium pK constants of macromolecules based upon their atomic resolution Protein Data Bank (PDB) structures; the calculations are often performed within the framework of the continuum electrostatics model. Unfortunately, these methodologies are complex, involve multiple steps and require considerable investment of effort. Our web server http://biophysics.cs.vt.edu/H++ provides access to a tool that automates this process, allowing both experts and novices to quickly obtain estimates of pKs as well as other related characteristics of biomolecules such as isoelectric points, titration curves and energies of protonation microstates. Protons are added to the input structure according to the calculated ionization states of its titratable groups at the user-specified pH; the output is in the PQR (PDB + charges + radii) format. In addition, corresponding coordinate and topology files are generated in the format supported by the molecular modeling package AMBER. The server is intended for a broad community of biochemists, molecular modelers, structural biologists and drug designers; it can also be used as an educational tool in biochemistry courses.
大分子的结构和功能严重依赖于其酸性和碱性基团的电离（质子化）状态。许多现有的实用方法基于大分子的原子分辨率蛋白质数据库（PDB）结构来预测质子化平衡pK常数；这些计算通常在连续介质静电模型的框架内进行。不幸的是，这些方法很复杂，涉及多个步骤，需要投入大量精力。我们的网络服务器http://biophysics.cs.vt.edu/H++提供了一个自动化此过程的工具，使专家和新手都能快速获得pK值的估计以及生物分子的其他相关特征，如等电点、滴定曲线和质子化微状态的能量。根据在用户指定pH下可滴定基团的计算电离状态，将质子添加到输入结构中；输出为PQR（PDB + 电荷 + 半径）格式。此外，还会以分子建模软件包AMBER支持的格式生成相应的坐标和拓扑文件。该服务器面向广大生物化学家、分子建模人员、结构生物学家和药物设计师群体；它也可用作生物化学课程中的教学工具。
