Simultaneous Identification of Multiple Binding Sites in Proteins: A Statistical Mechanics Approach
Simultaneous Identification of Multiple Binding Sites in Proteins: A Statistical Mechanics Approach
复制标题
同时鉴定蛋白质中的多个结合位点：统计力学方法
DOI：
10.1021/acs.jpcb.1c02658
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Orland, Henri
中科院分区：
文献类型：
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作者：
Koehl, Patrice;Delarue, Marc;Orland, Henri
我们提出了一个扩展的泊松-玻尔兹曼模型，其中感兴趣的溶质是沉浸在组装的自取向Langevin水偶极子，阴离子，阳离子和疏水分子，所有的可变密度。电荷之间的相互作用由静电控制，而疏水相互作用用汤川势建模。我们施加空间的限制，假设该系统是一个立方晶格。我们还假设不可压缩性;即，晶格的所有位置都被占据。这个模型，我们称之为疏水偶极泊松-玻尔兹曼朗之万（HDPBL）模型，导致两个方程的系统，其解决方案给出了水偶极子，盐和疏水分子的密度，所有这些都在存在的其他在一个自洽的方式。我们用它们来研究蛋白质周围的离子、共溶剂和溶剂分子的组织。特别地，期望密度的峰值同时揭示蛋白质上不同种类的相容结合位点的存在。我们已经测试并验证了HDPBL检测与疏水配体，极性配体和带电小探针结合的蛋白质中的口袋以及表征膜蛋白的脂质结合位点的能力。
We present an extension of the Poisson–Boltzmann model in which the solute of interest is immersed in an assembly of self-orienting Langevin water dipoles, anions, cations, and hydrophobic molecules, all of variable densities. Interactions between charges are controlled by electrostatics, while hydrophobic interactions are modeled with a Yukawa potential. We impose steric constraints by assuming that the system is represented on a cubic lattice. We also assume incompressibility; i.e., all sites of the lattice are occupied. This model, which we refer to as the Hydrophobic Dipolar Poisson–Boltzmann Langevin (HDPBL) model, leads to a system of two equations whose solutions give the water dipole, salt, and hydrophobic molecule densities, all of them in the presence of the others in a self-consistent way. We use those to study the organization of the ions, cosolvent, and solvent molecules around proteins. In particular, peaks of densities are expected to reveal, simultaneously, the presence of compatible binding sites of different kinds on a protein. We have tested and validated the ability of HDPBL to detect pockets in proteins that bind to hydrophobic ligands, polar ligands, and charged small probes as well as to characterize the binding sites of lipids for membrane proteins.