Sigalov Grigori, Fenley Andrew, Onufriev Alexey
Department of Computer Science, Virginia Tech, Blacksburg, Virginia 24061, USA.
J Chem Phys. 2006 Mar 28;124(12):124902. doi: 10.1063/1.2177251.
The modeling and simulation of macromolecules in solution often benefits from fast analytical approximations for the electrostatic interactions. In our previous work [G. Sigalov et al., J. Chem. Phys. 122, 094511 (2005)], we proposed a method based on an approximate analytical solution of the linearized Poisson-Boltzmann equation for a sphere. In the current work, we extend the method to biomolecules of arbitrary shape and provide computationally efficient algorithms for estimation of the parameters of the model. This approach, which we tentatively call ALPB here, is tested against the standard numerical Poisson-Boltzmann (NPB) treatment on a set of 579 representative proteins, nucleic acids, and small peptides. The tests are performed across a wide range of solvent/solute dielectrics and at biologically relevant salt concentrations. Over the range of the solvent and solute parameters tested, the systematic deviation (from the NPB reference) of solvation energies computed by ALPB is 0.5-3.5 kcal/mol, which is 5-50 times smaller than that of the conventional generalized Born approximation widely used in this context. At the same time, ALPB is equally computationally efficient. The new model is incorporated into the AMBER molecular modeling package and tested on small proteins.
溶液中大分子的建模与模拟常常受益于静电相互作用的快速解析近似方法。在我们之前的工作[G. Sigalov等人，《化学物理杂志》122, 094511 (2005)]中，我们提出了一种基于球体线性化泊松-玻尔兹曼方程近似解析解的方法。在当前工作中，我们将该方法扩展到任意形状的生物分子，并提供了计算效率高的算法来估计模型参数。这种方法，我们在此暂称为ALPB，在一组579个代表性蛋白质、核酸和小肽上与标准数值泊松-玻尔兹曼（NPB）处理方法进行了对比测试。测试在广泛的溶剂/溶质介电常数范围内以及生物学相关的盐浓度下进行。在所测试的溶剂和溶质参数范围内，ALPB计算的溶剂化能与NPB参考值的系统偏差为0.5 - 3.5千卡/摩尔，这比在此背景下广泛使用的传统广义玻恩近似的偏差小5 - 50倍。同时，ALPB在计算效率上同样出色。新模型已被纳入AMBER分子建模软件包，并在小蛋白质上进行了测试。
