Neves-Petersen Maria Teresa, Petersen Steffen B
Department of Physics and Nanotechnology, University of Aalborg, Biostructure and Protein Engineering Group, Sohngaardsholmsvej 49, DK-9000 Aalborg, Denmark.
Biotechnol Annu Rev. 2003;9:315-95. doi: 10.1016/s1387-2656(03)09010-0.
The molecular understanding of the initial interaction between a protein and, e.g., its substrate, a surface or an inhibitor is essentially an understanding of the role of electrostatics in intermolecular interactions. When studying biomolecules it is becoming increasingly evident that electrostatic interactions play a role in folding, conformational stability, enzyme activity and binding energies as well as in protein-protein interactions. In this chapter we present the key basic equations of electrostatics necessary to derive the equations used to model electrostatic interactions in biomolecules. We will also address how to solve such equations. This chapter is divided into two major sections. In the first part we will review the basic Maxwell equations of electrostatics equations called the Laws of Electrostatics that combined will result in the Poisson equation. This equation is the starting point of the Poisson-Boltzmann (PB) equation used to model electrostatic interactions in biomolecules. Concepts as electric field lines, equipotential surfaces, electrostatic energy and when can electrostatics be applied to study interactions between charges will be addressed. In the second part we will arrive at the electrostatic equations for dielectric media such as a protein. We will address the theory of dielectrics and arrive at the Poisson equation for dielectric media and at the PB equation, the main equation used to model electrostatic interactions in biomolecules (e.g., proteins, DNA). It will be shown how to compute forces and potentials in a dielectric medium. In order to solve the PB equation we will present the continuum electrostatic models, namely the Tanford-Kirkwood and the modified Tandord-Kirkwood methods. Priority will be given to finding the protonation state of proteins prior to solving the PB equation. We also present some methods that can be used to map and study the electrostatic potential distribution on the molecular surface of proteins. The combination of graphical visualisation of the electrostatic fields combined with knowledge about the location of key residues on the protein surface allows us to envision atomic models for enzyme function. Finally, we exemplify the use of some of these methods on the enzymes of the lipase family.
对蛋白质与其底物、表面或抑制剂之间初始相互作用的分子理解，本质上是对静电在分子间相互作用中所起作用的理解。在研究生物分子时，越来越明显的是，静电相互作用在折叠、构象稳定性、酶活性和结合能以及蛋白质 - 蛋白质相互作用中都发挥着作用。在本章中，我们将介绍推导用于模拟生物分子中静电相互作用的方程所需的关键静电学基本方程。我们还将讨论如何求解这些方程。本章分为两个主要部分。在第一部分中，我们将回顾静电学的基本麦克斯韦方程，即静电定律，这些方程组合起来将得到泊松方程。该方程是用于模拟生物分子中静电相互作用的泊松 - 玻尔兹曼（PB）方程的起点。我们将讨论电场线、等势面、静电能等概念，以及何时可以应用静电学来研究电荷之间的相互作用。在第二部分中，我们将推导适用于诸如蛋白质等介电介质的静电方程。我们将讨论电介质理论，并得出适用于介电介质的泊松方程和PB方程，这是用于模拟生物分子（如蛋白质、DNA）中静电相互作用的主要方程。我们将展示如何在介电介质中计算力和势。为了求解PB方程，我们将介绍连续介质静电模型，即坦福德 - 柯克伍德方法和改进的坦福德 - 柯克伍德方法。在求解PB方程之前，将优先确定蛋白质的质子化状态。我们还将介绍一些可用于绘制和研究蛋白质分子表面静电势分布的方法。静电场的图形可视化与蛋白质表面关键残基位置的知识相结合，使我们能够设想酶功能的原子模型。最后，我们举例说明其中一些方法在脂肪酶家族酶上的应用。
