A residue-pairwise generalized Born scheme suitable for protein design calculations
A residue-pairwise generalized Born scheme suitable for protein design calculations
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DOI：
10.1021/jp055282
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发表时间：
2005-12-01
影响因子：
3.3
通讯作者：
Simonson, T
中科院分区：
文献类型：
--
作者：
Archontis, G;Simonson, T
我们描述了一种有效的蛋白质广义Born(GB)近似，其中两个氨基酸之间的相互作用能取决于整个蛋白质结构，但可以根据残基对信息精确计算。两个结果使得该方案是成对的。首先，两个残基R和R‘之间的相互作用能存在一个精确的表达式，它取决于它们残基生成溶剂化半径的乘积B=BRBR’。其次，这个表达式被B的抛物线函数精确地拟合；(三)拟合系数只取决于对RR‘，而不是它的环境。实际上，量B捕获了与该对的介电环境相关的所有信息。该方法通过对数百种蛋白质Trpage、BPTI、泛素和索氧还蛋白结构的计算进行了测试。它产生的溶剂化能比传统的GB公式更符合泊松计算。我们还计算了蛋白质/溶剂环境对天冬氨酸氨基-tRNA合成酶活性部位带电残基之间相互作用的影响。我们的方法和传统的GB一样准确地捕捉到了这种效果。因为它是残基配对的，所以该方法可以被结合到用于旋转异构体放置和计算蛋白质设计的有效协议中。
We describe an efficient generalized Born (GB) approximation for proteins, in which the interaction energy between two amino acids depends on the whole protein structure, but can be accurately computed from residue-pairwise information. Two results make the scheme pairwise. First, an accurate expression exists for the interaction energy between two residues R and R' that depends on the product B = BRBR' of their residue Born solvation radii. Second, this expression is accurately fitted by a parabolic function of B; the (three) fitting coefficients depend only on the pair RR', not on its environment. In effect, the quantity B captures all the information that is relevant about the pair's dielectric environment. The method is tested with calculations on several hundred structures of the proteins trpcage, BPTI, ubiqutin, and thoredoxin. It yields solvation energies in better agreement with Poisson calculations than a traditional GB formulation. We also compute the effect of the protein/solvent environment on the interactions between pairs of charged residues in the active site of the enzyme aspartyl-tRNA synthetase. Our method captures this effect as accurately as traditional GB. Because it is residue-pairwise, the method can be incorporated into efficient protocols for rotamer placement and computational protein design.