J Chem Inf Model. 2019 Oct 28;59(10):4427-4437. doi: 10.1021/acs.jcim.9b00685. Epub 2019 Oct 15.
Noncovalent interactions between protein and DNA are important to comprehend different biological activities in living organisms. One important issue is how the protein identifies the target DNA and the influence of the resulting protein-DNA complex on the hydration environment around it. In this study, we have carried out atomistic molecular dynamics simulations of the protein-DNA complex formed by the dimeric form of the α-helical N-terminal domain of the λ-repressor protein with its operator DNA. Local heterogeneous flexibilities of the residues of the protein and the DNA components that are involved in binding and the microscopic structure and ordering of water around those have been investigated in detail. The calculations revealed concurrent existence of highly ordered as well as disordered water molecules at the interface. It is found that a fraction of doubly coordinated water molecules exhibit high degree of ordering at the interface, while the randomly oriented ones are coordinated with three water molecules. The effect has been found to be more around the protein and DNA residues that are in contact in the complexed state. We believe that such highly ordered two-coordinated water molecules are likely to act as an adhesive to facilitate the formation of a protein-DNA complex and maintain its structural stability.
蛋白质与 DNA 之间的非共价相互作用对于理解生物体内的不同生物活性非常重要。一个重要的问题是蛋白质如何识别靶 DNA 以及由此产生的蛋白质-DNA 复合物对其周围水合环境的影响。在这项研究中，我们对 λ 阻遏蛋白的二聚体形式的 α 螺旋 N 端结构域与其操纵子 DNA 形成的蛋白质-DNA 复合物进行了原子分子动力学模拟。详细研究了参与结合的蛋白质和 DNA 成分的局部不均匀柔韧性以及这些成分周围水的微观结构和有序性。计算结果表明，在界面处同时存在高度有序和无序的水分子。结果发现，一部分双配位水分子在界面处具有高度有序性，而随机取向的水分子则与三个水分子配位。这种影响在复合物中相互接触的蛋白质和 DNA 残基周围更为明显。我们相信，这种高度有序的双配位水分子可能起到粘着剂的作用，促进蛋白质-DNA 复合物的形成并维持其结构稳定性。
