Mierke D F, Kessler H
Organisch Chemisches Institut, Technische Universität München, Garching, Germany.
Biopolymers. 1993 Jul;33(7):1003-17. doi: 10.1002/bip.360330703.
In this article a few methods or modifications proven to be useful in the conformational examination of peptides and related molecules by molecular dynamics are illustrated. The first is the explicit use of organic solvents in the simulations. For many cases such solvents are appropriate since the nmr measurements (or other experimental observations) were carried out in the same solvent. Here, the use of dimethylsulfoxide and chloroform in molecular dynamics is described, with some advantages of the use of these solvents high-lighted. A constant allowing for the scaling of the nonbonded interactions of the force field, an idea previously employed in distance geometry and simulated annealing, has been implemented. The usefulness of this method is that when the nonbonded term is turned to zero, atoms can pass through each other, while the connectivity of the molecule is maintained. It will be shown that such simulations, if a sufficient driving force is present (i.e., nuclear Overhauser effects restraints), can produce the correct stereoconfiguration (i.e., chiral center) as well as configurational isomer (i.e., cis/trans isomers). Lastly, a penalty term for coupling constants directly related to the Karplus curve has been implemented into the potential energy force field. The advantages of this method over the commonly used dihedral angle restraining are discussed. In particular, it is shown that with more than one coupling constant about a dihedral angle a great reduction of the allowed conformational space is obtained.
本文阐述了几种经证实对通过分子动力学进行肽及相关分子构象研究有用的方法或改进方法。第一种是在模拟中明确使用有机溶剂。在许多情况下，此类溶剂是合适的，因为核磁共振测量（或其他实验观察）是在相同溶剂中进行的。这里描述了在分子动力学中使用二甲基亚砜和氯仿的情况，并强调了使用这些溶剂的一些优点。实现了一个用于缩放力场非键相互作用的常数，这是一个先前在距离几何和模拟退火中使用过的想法。该方法的有用之处在于，当非键项变为零时，原子可以相互穿过，同时保持分子的连接性。结果表明，如果存在足够的驱动力（即核Overhauser效应约束），此类模拟可以产生正确的立体构型（即手性中心）以及构型异构体（即顺式/反式异构体）。最后，一个与Karplus曲线直接相关的耦合常数惩罚项已被引入势能力场。讨论了该方法相对于常用的二面角约束的优点。特别指出，对于围绕一个二面角有多个耦合常数的情况，可以大大减少允许的构象空间。
