Heiner A P, Berendsen H J, van Gunsteren W F
Laboratory of Physical Chemistry, University of Groningen, The Netherlands.
Proteins. 1992 Dec;14(4):451-64. doi: 10.1002/prot.340140406.
In this paper we present a molecular dynamics (MD) simulation of subtilisin BPN' in a crystalline environment containing four protein molecules and solvent. Conformational and dynamic properties of the molecules are compared with each other and with respect to the X-ray structure to test the validity of the force field. The agreement between simulated and experimental structure using the GROMOS force field is better than that obtained in the literature using other force fields for protein crystals. The overall shape of the molecule is well preserved, as is the conformation of alpha-helices and beta-strands. Structural differences are mainly found in loop regions. Solvent networks found in the X-ray structure were reproduced by the simulation, which was unbiased with respect to the crystalline hydration structure. These networks seem to play an important role in the stability of the protein; evidence of this is found in the structure of the active site. The weak ion binding site in the X-ray structure of subtilisin BPN' is occupied by a monovalent ion. When a calcium ion is placed in the initial structure, three peptide ligands are replaced by 5 water ligands, whereas a potassium ion retains (in part) its original ligands. Existing force fields yield a reliable method to probe local structure and short-time dynamics of proteins, providing an accuracy of about 0.1 nm.
在本文中，我们展示了在含有四个蛋白质分子和溶剂的晶体环境中枯草杆菌蛋白酶BPN'的分子动力学（MD）模拟。将分子的构象和动力学性质相互比较，并与X射线结构进行比较，以测试力场的有效性。使用GROMOS力场的模拟结构与实验结构之间的一致性优于文献中使用其他力场对蛋白质晶体所获得的一致性。分子的整体形状以及α螺旋和β链的构象都得到了很好的保留。结构差异主要出现在环区。模拟重现了X射线结构中发现的溶剂网络，该模拟对晶体水合结构没有偏差。这些网络似乎在蛋白质的稳定性中起重要作用；在活性位点的结构中发现了这方面的证据。枯草杆菌蛋白酶BPN'的X射线结构中的弱离子结合位点被一价离子占据。当在初始结构中放置一个钙离子时，三个肽配体被五个水配体取代，而一个钾离子（部分）保留其原始配体。现有的力场提供了一种可靠的方法来探测蛋白质的局部结构和短时间动力学，精度约为0.1纳米。
