Analysis of fast boundary-integral approximations for modeling electrostatic contributions of molecular binding.
Analysis of fast boundary-integral approximations for modeling electrostatic contributions of molecular binding.
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DOI：
10.2478/mlbmb-2013-0007
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发表时间：
2013-06
影响因子：
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通讯作者：
Radhakrishnan ML
中科院分区：
文献类型：
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作者：
Kreienkamp AB;Liu LY;Minkara MS;Knepley MG;Bardhan JP;Radhakrishnan ML
我们分析和建议改进最近开发的蛋白质近似连续静电模型。该模型，被称为BIBEE/I（边界积分为基础的静电插值估计），是能够估计静电溶剂化自由能的平均无符号误差为4%的测试集上超过600蛋白质的显着改善比以前的BIBEE模型。在这项工作中，我们测试了BIBEE/I模型预测蛋白质-蛋白质结合中残基相互作用的能力，使用广泛研究的胰蛋白酶和牛胰蛋白酶抑制剂（BPTI）模型系统。发现BIBEE/I模型在这项任务中的表现令人惊讶地不如简单的BIBEE模型，我们试图解释这种行为的模型的不同谱近似的精确边界积分算子。解析可解系统（球体和三轴椭球）的计算提出了两种改进的可能性。第一个是一个修改的BIBEE/我的方法，捕获的渐近本征值极限正确，第二个涉及的偶极和四极模式的椭圆近似的蛋白质几何形状。我们的分析表明，快速，严格的近似模型来自减少基础近似的边界积分方程可能会达到前所未有的准确性，如果偶极和四极模式可以迅速捕获一般形状。
We analyze and suggest improvements to a recently developed approximate continuum-electrostatic model for proteins. The model, called BIBEE/I (boundary-integral based electrostatics estimation with interpolation), was able to estimate electrostatic solvation free energies to within a mean unsigned error of 4% on a test set of more than 600 proteins—a significant improvement over previous BIBEE models. In this work, we tested the BIBEE/I model for its capability to predict residue-by-residue interactions in protein–protein binding, using the widely studied model system of trypsin and bovine pancreatic trypsin inhibitor (BPTI). Finding that the BIBEE/I model performs surprisingly less well in this task than simpler BIBEE models, we seek to explain this behavior in terms of the models’ differing spectral approximations of the exact boundary-integral operator. Calculations of analytically solvable systems (spheres and tri-axial ellipsoids) suggest two possibilities for improvement. The first is a modified BIBEE/I approach that captures the asymptotic eigenvalue limit correctly, and the second involves the dipole and quadrupole modes for ellipsoidal approximations of protein geometries. Our analysis suggests that fast, rigorous approximate models derived from reduced-basis approximation of boundary-integral equations might reach unprecedented accuracy, if the dipole and quadrupole modes can be captured quickly for general shapes.