Department of Biochemistry, Federal University Oye-Ekiti, Oye-Ekiti, Ekiti State, Nigeria.
J Biomol Struct Dyn. 2023 Jul;41(10):4398-4404. doi: 10.1080/07391102.2022.2067240. Epub 2022 Apr 26.
Human 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR; EC 1.1.1.34) catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, which has been defined as the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus playing a critical role in cellular cholesterol homeostasis. In this study, the effect of changing pH on the structural dynamics and binding affinity of HMGCR were investigated by molecular dynamics simulation using OpenMM, and molecular docking using Autodock Vina. The results pinpoint pH 8.0 for optimum structural stability/activity of HMGCR, and the insightful relationships between pH, structural dynamics radius of gyration (Rg) or root mean square deviation (RMSD), and binding affinity of HMGCR. This method will be useful to predict the pH for the uncharacterized human proteins, toward biomedical and biotechnological applicationsCommunicated by Ramaswamy H. Sarma.
人 3-羟基-3-甲基戊二酰辅酶 A 还原酶（HMGCR；EC 1.1.1.34）催化（3S）-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）转化为甲羟戊酸，这已被定义为胆固醇和其他异戊二烯合成的限速步骤，因此在细胞胆固醇稳态中起着关键作用。在这项研究中，使用 OpenMM 通过分子动力学模拟和 Autodock Vina 进行分子对接来研究 pH 值变化对 HMGCR 结构动力学和结合亲和力的影响。结果确定了 pH 8.0 是 HMGCR 最佳结构稳定性/活性的条件，并确定了 pH 值与 HMGCR 的结构动力学半径 gyration（Rg）或均方根偏差（RMSD）和结合亲和力之间的关系。这种方法将有助于预测未表征的人类蛋白质的 pH 值，以应用于生物医学和生物技术。由 Ramaswamy H. Sarma 传达。
