Brownian dynamics simulation of protein association.
Brownian dynamics simulation of protein association.
复制标题
蛋白质关联的布朗动力学模拟。
DOI：
10.1007/bf01677278
复制
发表时间：
1988
影响因子：
3.5
通讯作者：
Reynolds,JC
中科院分区：
文献类型：
--
作者：
Northrup,SH;Luton,JA;Boles,JO;Reynolds,JC
应用布朗动力学（BD）方法研究了细胞色素c（CYTC）和细胞色素c过氧化物酶（CYPC）两种蛋白质的扩散动力学和相互作用。我们研究了蛋白质静电荷分布在电子转移步骤之前促进蛋白质-蛋白质对接中的作用，评估了单个带电氨基酸残基的影响。精确的相互作用势计算通过迭代的线性化泊松-玻尔兹曼（PB）方程周围的较大的蛋白质分子。考虑到蛋白质内部的低介电常数、电解质屏蔽效应和不规则的蛋白质表面形貌。我们观察到一个大的合奏静电稳定的遭遇复杂的电子转移，而不是一个单一的主导复杂的似乎与可接受的几何要求。各种各样的对接复合物的稳定性是合理的广义带电残基互补性。然而，它被发现，静电相互作用引起的复杂的稳定性是有点非特异性的性质。进行了大量的额外模拟，其中CYTC上的单个带电残基已被化学修饰。由此产生的扰动的关联率是显着的，定性类似于在可比的动力学实验中观察到的结果。因此，我们证明了潜在的布朗动力学方法来估计定点诱变对蛋白质-蛋白质和蛋白质-配体扩散缔合速率的影响。
The Brownian Dynamics (BD) method is applied to study the diffusive dynamics and interaction of two proteins, cytochrome c (CYTC) and cytochrome c peroxidase (CYP). We examine the role of protein electrostatic charge distribution in the facilitation of protein-protein docking prior to the electron transfer step, assessing the influence of individual charged amino acid residues. Accurate interaction potentials are computed by iterating the linearized Poisson-Boltzmann (PB) equation around the larger protein CYP. The low dielectric constant inside proteins, electrolyte screening effects and irregular protein surface topography are taken into account. We observe a large ensemble of electrostatically stable encounter complexes seemingly with acceptable geometric requirements for electron transfer rather than a single dominant complex. Stabilities of the large variety of docking complexes are rationalized in terms of generalized charged residue complementarities. However, it is found that the electrostatic interactions giving rise to complex stabilities are somewhat nonspecific in nature. A large series of additional simulations are performed in which individual charged residues on CYTC have been chemically modified. Resulting perturbations of the association rate are significant and qualitatively similar to results observed in comparable kinetics experiments. We therefore demonstrate the potential of the Brownian dynamics method to estimate the effects of site-directed mutagenesis on protein-protein and protein-ligand diffusional association rates.