Modification of the generalized Born model suitable for macromolecules
Modification of the generalized Born model suitable for macromolecules
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DOI：
10.1021/jp994072s
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发表时间：
2000-04-20
影响因子：
3.3
通讯作者：
Case, DA
中科院分区：
文献类型：
--
作者：
Onufriev, A;Bashford, D;Case, DA
解析广义玻恩近似是描述溶液中分子的有效静电模型。在这里，它被修改，以允许更准确地描述大的高分子，而其建立的小化合物的性能几乎不受影响。修改后的模型也适用于描述分子的内部介电常数不等于单位。该模型进行了测试，通过计算的pK位移的溶菌酶，肌红蛋白，和细菌视紫红质中的一些可滴定的残留物。在一般情况下，除了一些深埋的残留物的细菌视紫红质，结果显示合理的协议与实验数据和计算的基础上的Poisson-Boltzmann方程的数值解。一个非常接近的协议之间的两个模型得到的应用程序中的预测与构象变化相关的pK位移。基于该版本的广义玻恩近似的计算比Poisson-Boltzmann方程的有限差分解快得多，这使得本方法可用于计算时间是关键因素的各种其他应用。该模型也可以集成到分子动力学程序，以取代显式溶剂模拟，这是特别耗时的大分子。
The analytic generalized Born approximation is an efficient electrostatic model that describes molecules in solution. Here it is modified to permit a more accurate description of large macromolecules, while its established performance on small compounds is nearly unaffected. The modified model is also adapted to describe molecules with an interior dielectric constant not equal to unity. The model is tested by computations of pK shifts for a number of titratable residues in lysozyme, myoglobin, and bacteriorhodopsin. In general, except for some deeply buried residues of bacteriorhodopsin, the results show reasonable agreement with both experimental data and calculations based on numerical solution of the Poisson-Boltzmann equation. A very close agreement between the two models is obtained in an application to the prediction of the pK shifts associated with conformational change. The calculations based on this version of the generalized Born approximation are much faster than finite difference solutions of the Poisson-Boltzmann equation, which makes the present method useful for a variety of other applications where computational time is a critical factor. The model may also be integrated into molecular dynamics programs to replace explicit solvent simulations which are particularly time-consuming for large molecules.