通过数据丰富的静电计算揭示膜蛋白特性
Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.
作者信息
Marcoline Frank V, Bethel Neville, Guerriero Christopher J, Brodsky Jeffrey L, Grabe Michael
机构信息
Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA.
Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA; Integrative Program in Quantitative Biology, University of California, San Francisco, CA 94158, USA.
出版信息
Structure. 2015 Aug 4;23(8):1526-1537. doi: 10.1016/j.str.2015.05.014. Epub 2015 Jun 25.
The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information.
膜蛋白的静电特性往往揭示出许多关键的生物物理特征，如离子通道选择性和带电跨膜片段的稳定性。泊松-玻尔兹曼（PB）方程是计算蛋白质静电的金标准，而软件APBSmem能够在有膜存在的情况下求解PB方程。在此，我们描述了APBSmem的重大进展，包括系统设置的完全自动化、按残基的能量分解、整合PDB2PQR、计算膜诱导的pKa位移、计算非极性能量以及用于大规模计算的命令行脚本。我们通过对多种膜蛋白进行计算来突出这些新特性，其中包括最近解析出结构的离子通道TRPV1以及对1614种已知结构的膜蛋白进行的大规模研究。这项研究提供了一份在嵌入膜中时具有较大静电罚分的残基的综合列表，可能揭示出有趣的功能信息。
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