Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
J Phys Chem B. 2012 Mar 8;116(9):2958-68. doi: 10.1021/jp209437j. Epub 2012 Feb 24.
Free energy barriers separating interfacial water molecules from the hydration layer at the surface of a protein to the bulk are obtained by using the umbrella sampling method of free energy calculation. We consider hydration layer of chicken villin head piece (HP-36) which has been studied extensively by molecular dynamics simulations. The free energy calculations reveal a strong sensitivity to the secondary structure. In particular, we find a region near the junction of first and second helix that contains a cluster of water molecules which are slow in motion, characterized by long residence times (of the order of 100 ps or more) and separated by a large free energy barrier from the bulk water. However, these "slow" water molecules constitute only about 5-10% of the total number of hydration layer water molecules. Nevertheless, they play an important role in stabilizing the protein conformation. Water molecules near the third helix (which is the important helix for biological function) are enthalpically least stable and exhibit the fastest dynamics. Interestingly, barrier height distributions of interfacial water are quite broad for water surrounding all the three helices (and the three coils), with the smallest barriers found for those near the helix-3. For the quasi-bound water molecules near the first and second helices, we use well-known Kramers' theory to estimate the residence time from the free energy surface, by estimating the friction along the reaction coordinate from the diffusion coefficient by using Einstein relation. The agreement found is satisfactory. We discuss the possible biological function of these slow, quasi-bound (but transient) water molecules on the surface.
通过自由能计算的伞形采样方法，获得了将界面水分子与蛋白质表面水合层分离到体相的自由能势垒。我们考虑了鸡绒毛蛋白头部片段（HP-36）的水合层，该水合层已经通过分子动力学模拟进行了广泛研究。自由能计算对二级结构表现出很强的敏感性。特别是，我们在第一和第二螺旋的交界处附近发现了一个水分子簇，这些水分子运动缓慢，特征是停留时间长（约 100 ps 或更长），与体相水之间存在很大的自由能势垒。然而，这些“慢”水分子仅占水合层水分子总数的 5-10%左右。尽管如此，它们在稳定蛋白质构象方面起着重要作用。靠近第三螺旋（对生物功能很重要的螺旋）的水分子在焓上最不稳定，表现出最快的动力学。有趣的是，围绕所有三个螺旋（和三个线圈）的界面水的势垒高度分布相当宽，在靠近螺旋-3 的那些水的势垒最小。对于靠近第一和第二螺旋的准束缚水分子，我们使用著名的 Kramer 理论，通过使用爱因斯坦关系从扩散系数估算沿反应坐标的摩擦，从自由能表面估算停留时间。发现的结果是令人满意的。我们讨论了这些表面上缓慢、准束缚（但瞬态）水分子的可能生物学功能。
