Gerstein M, Tsai J, Levitt M
Department of Structural Biology, Standford University, CA 94305, USA.
J Mol Biol. 1995 Jun 23;249(5):955-66. doi: 10.1006/jmbi.1995.0351.
We analyze the volume of atoms on the protein surface during a molecular-dynamics simulation of a small protein (pancreatic trypsin inhibitor). To calculate volumes, we use a particular geometric construction, called Voronoi polyhedra, that divides the total volume of the simulation box amongst the atoms, rendering them relatively larger or smaller depending on how tightly they are packed. We find that most of the atoms on the protein surface are larger than those buried in the core (by approximately 6%), except for the charged atoms, which decrease in size, presumably due to electroconstriction. We also find that water molecules are larger near apolar atoms on the protein surface and smaller near charged atoms, in comparison to "bulk" water molecules far from the protein. Taken together, these findings necessarily imply that apolar atoms on the protein surface and their associated water molecules are less tightly packed (than corresponding atoms in the protein core and bulk water) and the opposite is the case for charged atoms. This looser apolar packing and tighter charged packing fundamentally reflects protein-water distances that are larger or smaller than those expected from van der Waals radii. In addition to the calculation of mean volumes, simulations allow us to investigate the volume fluctuations and hence compressibilities of the protein and solvent atoms. The relatively large volume fluctuations of atoms at the protein-water interface indicates that they have a more variable packing than corresponding atoms in the protein core or in bulk water. We try to adhere to traditional conventions throughout our calculations. Nevertheless, we are aware of and discuss three complexities that significantly qualify our calculations: the positioning of the dividing plane between atoms, the problem of vertex error, and the choice of atom radii. In particular, our results highlight how poor a "compromise" the commonly accepted value of 1.4 A is for the radius of a water molecule.
在对一种小蛋白质（胰蛋白酶抑制剂）进行分子动力学模拟的过程中，我们分析了蛋白质表面原子的体积。为了计算体积，我们使用了一种特殊的几何结构，即Voronoi多面体，它将模拟盒的总体积在原子之间进行划分，根据原子的紧密堆积程度使其相对变大或变小。我们发现，蛋白质表面的大多数原子比埋在核心区域的原子大（约6%），但带电原子除外，其尺寸减小，推测是由于电收缩效应。我们还发现，与远离蛋白质的“体相”水分子相比，蛋白质表面非极性原子附近的水分子较大，而带电原子附近的水分子较小。综合来看，这些发现必然意味着蛋白质表面的非极性原子及其相关水分子的堆积较松散（相比于蛋白质核心区域的相应原子和体相水），而带电原子的情况则相反。这种较松散的非极性堆积和较紧密的带电堆积从根本上反映了蛋白质与水之间的距离大于或小于范德华半径所预期的距离。除了计算平均体积外，模拟还使我们能够研究体积波动，进而研究蛋白质和溶剂原子的压缩性。蛋白质 - 水界面处原子相对较大的体积波动表明，它们的堆积比蛋白质核心区域或体相水中的相应原子更具变化性。在整个计算过程中，我们尽量遵循传统惯例。然而，我们意识到并讨论了三个显著影响我们计算的复杂因素：原子间分隔平面的定位、顶点误差问题以及原子半径的选择。特别是，我们的结果突出了普遍接受的1.4 Å作为水分子半径是多么不合适。
