Steinbuch Centre for Computing, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Comput Biol Chem. 2011 Aug 10;35(4):230-9. doi: 10.1016/j.compbiolchem.2011.04.012. Epub 2011 May 27.
The presence of disulfide bonds in proteins has very important implications on the three-dimensional structure and folding of proteins. An adequate treatment of disulfide bonds in de-novo protein simulations is therefore very important. Here we present a computational study of a set of small disulfide-bridged proteins using an all-atom stochastic search approach and including various constraining potentials to describe the disulfide bonds. The proposed potentials can easily be implemented in any code based on all-atom force fields and employed in simulations to achieve an improved prediction of protein structure. Exploring different potential parameters and comparing the structures to those from unconstrained simulations and to experimental structures by means of a scoring function we demonstrate that the inclusion of constraining potentials improves the quality of final structures significantly. For some proteins (1KVG and 1PG1) the native conformation is visited only in simulations in presence of constraints. Overall, we found that the Morse potential has optimal performance, in particular for the β-sheet proteins.
蛋白质中二硫键的存在对蛋白质的三维结构和折叠有非常重要的影响。因此，在从头计算蛋白质模拟中充分考虑二硫键非常重要。在这里，我们使用全原子随机搜索方法对一组小的二硫键桥接蛋白质进行了计算研究，并包括各种约束势来描述二硫键。所提出的势能可以很容易地在任何基于全原子力场的代码中实现，并在模拟中使用，以提高对蛋白质结构的预测能力。通过探索不同的势能参数，并通过评分函数将结构与无约束模拟和实验结构进行比较，我们证明了约束势的加入显著提高了最终结构的质量。对于一些蛋白质（1KVG 和 1PG1），只有在存在约束的情况下，模拟才能访问其天然构象。总的来说，我们发现莫尔斯势能的性能最佳，特别是对于β-折叠蛋白质。
