Pezzella Marco, El Hage Krystel, Niesen Michiel J M, Shin Sucheol, Willard Adam P, Meuwly Markus, Karplus Martin
Department of Chemistry, University of Basel, Klingelbergstrasse 80, CH-4056 Basel, Switzerland.
SABNP, Université Evry, INSERM U1204, Université Paris-Saclay, 91025 Evry, France.
J Phys Chem B. 2020 Jul 30;124(30):6540-6554. doi: 10.1021/acs.jpcb.0c04320. Epub 2020 Jul 20.
The water dynamics, as characterized by the local hydrophobicity (LH), is investigated for tetrameric hemoglobin (Hb) and dimeric melittin. For the T to R transition in Hb, it is found that LH provides additional molecular-level insight into the Perutz mechanism, i.e., the breaking and formation of salt bridges at the α/β and α/β interface is accompanied by changes in LH. For Hb in cubic water boxes with 90 and 120 Å edge length it is observed that following a decrease in LH as a consequence of reduced water density or change of water orientation at the protein/water interface the α/β interfaces are destabilized; this is a hallmark of the Perutz stereochemical model for the T to R transition in Hb. The present work thus provides a dynamical view of the classical structural model relevant to the molecular foundations of Hb function. For dimeric melittin, earlier results by Cheng and Rossky [ 1998, 392, 696-699] are confirmed and interpreted on the basis of LH from simulations in which the protein structure is frozen. For the flexible melittin dimer, the changes in the local hydration can be as much as 30% greater than for the rigid dimer, reflecting the fact that protein and water dynamics are coupled.
通过局部疏水性（LH）表征的水动力学，针对四聚体血红蛋白（Hb）和二聚体蜂毒肽进行了研究。对于Hb中T态到R态的转变，发现LH为佩鲁茨机制提供了额外的分子水平见解，即α/β和α/β界面处盐桥的断裂和形成伴随着LH的变化。在边长为90 Å和120 Å的立方水盒中的Hb，观察到由于蛋白质/水界面处水密度降低或水取向改变导致LH降低后，α/β界面不稳定；这是Hb中T态到R态转变的佩鲁茨立体化学模型的一个标志。因此，本工作提供了与Hb功能分子基础相关的经典结构模型的动力学观点。对于二聚体蜂毒肽，程和罗斯基[1998, 392, 696 - 699]的早期结果在蛋白质结构固定的模拟中基于LH得到了证实和解释。对于柔性蜂毒肽二聚体，局部水合作用的变化可能比刚性二聚体大30%，这反映了蛋白质和水动力学是相互耦合的这一事实。
