Naddaf Lamis, Sayyed-Ahmad Abdallah
Department of Physics, Birzeit University, Birzeit, Palestine.
Department of Physics, Birzeit University, Birzeit, Palestine.
Arch Biochem Biophys. 2014 Dec 15;564:12-9. doi: 10.1016/j.abb.2014.08.016. Epub 2014 Sep 8.
The dimerization rate of the bacterial cell division protein FtsZ is strongly affected by the intracellular crowding. Yet the complexity of the intracellular environment makes it difficult to investigate via all-atom molecular dynamics or other detailed theoretical methods. We study the crowding effect on FtsZ dimerization which is the first step of an oligomerization process that results in more elaborate supramolecular structures. In particular, we consider the effect of intracellular crowding on the reaction rates, and their dependence on the different concentrations of crowding agents. We achieved this goal by using Brownian dynamics (BD) simulation techniques and a modified post-processing approach in which we decompose the rate constant in crowded media as a product of the rate constant in the dilute solution times a factor that incorporates the crowding effect. The latter factor accounts for the diffusion reduction and crowder induced energy. In addition we include the crowding effects on water viscosity in the BD simulations of crowded media. We finally show that biomolecular crowding has a considerable effect on the FtsZ dimerization by increasing the dimerization rate constant from 2.6×10(7)M(-1)s(-1) in the absence of crowders to 1.0×10(8)M(-1)s(-1) at crowding level of 0.30.
细菌细胞分裂蛋白FtsZ的二聚化速率受到细胞内拥挤效应的强烈影响。然而，细胞内环境的复杂性使得通过全原子分子动力学或其他详细的理论方法进行研究变得困难。我们研究了拥挤效应对FtsZ二聚化的影响，这是一个导致更复杂超分子结构的寡聚化过程的第一步。特别是，我们考虑了细胞内拥挤对反应速率的影响，以及它们对不同浓度拥挤剂的依赖性。我们通过使用布朗动力学（BD）模拟技术和一种改进的后处理方法实现了这一目标，在该方法中，我们将拥挤介质中的速率常数分解为稀溶液中速率常数与一个包含拥挤效应的因子的乘积。后一个因子考虑了扩散减少和拥挤剂诱导的能量。此外，我们在拥挤介质的BD模拟中考虑了拥挤对水粘度的影响。我们最终表明，生物分子拥挤通过将二聚化速率常数从无拥挤剂时的2.6×10⁷M⁻¹s⁻¹提高到拥挤水平为0.30时的1.0×10⁸M⁻¹s⁻¹，对FtsZ二聚化有相当大的影响。
