MOE Key Lab of Bioinformatics, Institute of Bioinformatics and System Biology, School of Life Science, Tsinghua University, Beijing, China.
Biophys J. 2010 Feb 3;98(3):470-7. doi: 10.1016/j.bpj.2009.10.031.
Born-type electrostatic continuum methods have been an indispensable ingredient in a variety of implicit-solvent methods that reduce computational effort by orders of magnitude compared to explicit-solvent MD simulations and thus enable treatment using larger systems and/or longer times. An analysis of the limitations and failures of the Born approaches serves as a guide for fundamental improvements without diminishing the importance of prior works. One of the major limitations of the Born theory is the lack of a liquidlike description of the response of solvent dipoles to the electrostatic field of the solute and the changes therein, a feature contained in the continuum Langevin-Debye (LD) model applied here to investigate how Coulombic interactions depend on the location of charges relative to the protein/water boundary. This physically more realistic LD model is applied to study the stability of salt bridges. When compared head to head using the same (independently measurable) physical parameters (radii, dielectric constants, etc.), the LD model is in good agreement with observations, whereas the Born model is grossly in error. Our calculations also suggest that a salt bridge on the protein's surface can be stabilizing when the charge separation is < or =4 A.
Born 型静电连续体方法是各种隐溶剂方法中不可或缺的组成部分，与显溶剂 MD 模拟相比，这些方法可将计算工作量降低几个数量级，从而能够处理更大的系统和/或更长的时间。对 Born 方法的局限性和失败的分析为基本改进提供了指导，而不会降低先前工作的重要性。Born 理论的主要局限性之一是缺乏对溶剂偶极子对溶质和其中变化的电场的液态描述，这一特征包含在连续体 Langevin-Debye (LD) 模型中，该模型用于研究库仑相互作用如何取决于电荷相对于蛋白质/水边界的位置。这种物理上更现实的 LD 模型被应用于研究盐桥的稳定性。当使用相同的（可独立测量的）物理参数（半径、介电常数等）进行正面比较时，LD 模型与观察结果非常吻合，而 Born 模型则存在严重错误。我们的计算还表明，当电荷分离<或=4 A 时，蛋白质表面上的盐桥可以是稳定的。
