Abstract：
The dynamics of DNA gyrase and mutants of DNA gyrA such as G88A, A90V, S91P, D94A, D94G, D94N, D94Y; and double-point mutant (S91P-D94G), are meticulously investigated using computational approaches. Molecular dynamics (MD) and hydration thermodynamics have shed light on the fundamental, mechanistic basis of mutations on the conformational stability of Quinolone Binding Pocket (QBP) of DNA gyrase. Analysis of MD results revealed the displacement of a single crystal water molecule (HOH201) from the catalytic site of wild-type (WT) and mutants of DNA gyrA. This prompted our research group to probe the five crystal water molecules present in the QBP of the enzyme using water thermodynamics. Hydration thermodynamics analysis revealed the displacement of HOH201 due to unstable thermodynamic signatures. Further, the analysis highlighted significant changes in thermodynamic signatures and locations of five crystal water hydration sites upon mutation. Integrated MD simulations and water thermodynamics provided promising insights into the conformational changes and inaccessibility of the catalytic water molecule that can influence the design of DNA gyrase inhibitors.Communicated by Ramaswamy H. Sarma.
摘要：
DNA促旋酶和DNAgyrA突变体如G88A的动力学，A90V,S91P,D94A,D94G,D94N,D94Y;和双点突变体(S91P-D94G),使用计算方法进行精心研究。分子动力学(MD)和水合热力学揭示了DNA促旋酶的喹诺酮结合袋（QBP）构象稳定性的突变机理。MD结果的分析表明，单晶水分子（HOH201）从野生型（WT）的催化位点和DNAgyrA的突变体中置换。这促使我们的研究小组使用水热力学来探测酶的QBP中存在的五个结晶水分子。水合热力学分析显示，由于热力学特征不稳定，HOH201的位移。Further,分析强调了突变后五个结晶水水合位点的热力学特征和位置的显着变化。集成的MD模拟和水热力学为可能影响DNA促旋酶抑制剂设计的催化水分子的构象变化和不可接近性提供了有希望的见解。由RamaswamyH.Sarma沟通。
