关于溶剂对蛋白质电离常数影响的准确的、构象依赖性预测。
Accurate, conformation-dependent predictions of solvent effects on protein ionization constants.
作者信息
Barth P, Alber T, Harbury P B
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3206, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4898-903. doi: 10.1073/pnas.0700188104. Epub 2007 Mar 14.
Abstract
Predicting how aqueous solvent modulates the conformational transitions and influences the pKa values that regulate the biological functions of biomolecules remains an unsolved challenge. To address this problem, we developed FDPB_MF, a rotamer repacking method that exhaustively samples side chain conformational space and rigorously calculates multibody protein-solvent interactions. FDPB_MF predicts the effects on pKa values of various solvent exposures, large ionic strength variations, strong energetic couplings, structural reorganizations and sequence mutations. The method achieves high accuracy, with root mean square deviations within 0.3 pH unit of the experimental values measured for turkey ovomucoid third domain, hen lysozyme, Bacillus circulans xylanase, and human and Escherichia coli thioredoxins. FDPB_MF provides a faithful, quantitative assessment of electrostatic interactions in biological macromolecules.
摘要
预测水性溶剂如何调节构象转变并影响调节生物分子生物学功能的pKa值仍然是一个尚未解决的挑战。为了解决这个问题，我们开发了FDPB_MF，这是一种旋转异构体重新排列方法，它能详尽地对侧链构象空间进行采样，并严格计算多体蛋白质-溶剂相互作用。FDPB_MF预测了各种溶剂暴露、大离子强度变化、强能量耦合、结构重组和序列突变对pKa值的影响。该方法具有很高的准确性，对于火鸡卵类粘蛋白第三结构域、母鸡溶菌酶、环状芽孢杆菌木聚糖酶以及人和大肠杆菌硫氧还蛋白，其均方根偏差在实验值的0.3 pH单位范围内。FDPB_MF对生物大分子中的静电相互作用提供了可靠的定量评估。
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