Madhusudhan M S, Vishveshwara S
Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Biopolymers. 1999 Feb;49(2):131-44. doi: 10.1002/(SICI)1097-0282(199902)49:2<131::AID-BIP3>3.0.CO;2-W.
Molecular dynamics simulations have been carried out for 1 ns on human and bovine angiogenin systems in an effort to compare and contrast their dynamics. An analysis of their dynamics is done by examining the rms deviations, following hydrogen-bonding interactions and looking at the role of water in and around the protein. The C-terminus of bovine angiogenin moves appreciably during dynamics suggesting a better structure for ligand binding. However, we do not find any evidence of a conformation where the glutamate residue that obstructs the active site takes on a different conformation. We observe a differential hydrogen-bonding pattern in the active site regions of bovine and human angiogenins, which could have a bearing on the different catalytic activities of the proteins. We also propose that the differential binding of the monoclonal antibody toward the two proteins might be due sequential and not conformational differences. Water molecules might play an important functional role in both proteins given their subtle functional differences. A simple computation on the molecular dynamics data has been carried out to identify locations in and around the protein that are invariably occupied by water. The locations of nearly half the waters we have identified from the simulation as being invariant in bovine angiogenin occupy similar locations in the bovine angiogenin crystal structure. The positions of the waters identified in human angiogenin differ considerably from that of bovine angiogenin.
为了比较和对比人血管生成素和牛血管生成素系统的动力学，对其进行了1纳秒的分子动力学模拟。通过检查均方根偏差、跟踪氢键相互作用以及观察蛋白质内部和周围水的作用来分析它们的动力学。牛血管生成素的C末端在动力学过程中明显移动，这表明其具有更好的配体结合结构。然而，我们没有发现阻碍活性位点的谷氨酸残基呈现不同构象的任何证据。我们观察到牛血管生成素和人血管生成素活性位点区域存在不同的氢键模式，这可能与蛋白质的不同催化活性有关。我们还提出，单克隆抗体对这两种蛋白质的不同结合可能是由于序列差异而非构象差异。鉴于它们细微的功能差异，水分子可能在这两种蛋白质中都发挥着重要的功能作用。对分子动力学数据进行了简单计算，以确定蛋白质内部和周围始终被水占据的位置。我们从模拟中确定的牛血管生成素中近一半不变的水分子位置，在牛血管生成素晶体结构中占据相似位置。人血管生成素中确定的水分子位置与牛血管生成素的位置有很大差异。
