Physik-Department T38, Technische Universität München, James Franck Str. 1, 85748 Garching, Germany.
Proteins. 2013 Jan;81(1):81-92. doi: 10.1002/prot.24164. Epub 2012 Sep 26.
A hybrid coarse-grained (CG) and atomistic (AT) model for protein simulations and rapid searching and refinement of peptide-protein complexes has been developed. In contrast to other hybrid models that typically represent spatially separate parts of a protein by either a CG or an AT force field model, the present approach simultaneously represents the protein by an AT (united atom) and a CG model. The interactions of the protein main chain are described based on the united atom force field allowing a realistic representation of protein secondary structures. In addition, the AT description of all other bonded interactions keeps the protein compatible with a realistic bonded geometry. Nonbonded interactions between side chains and side chains and main chain are calculated at the level of a CG model using a knowledge-based potential. Unrestrained molecular dynamics simulations on several test proteins resulted in trajectories in reasonable agreement with the corresponding experimental structures. Applications to the refinement of docked peptide-protein complexes resulted in improved complex structures. Application to the rapid refinement of docked protein-protein complex is also possible but requires further optimization of force field parameters.
已经开发出一种用于蛋白质模拟的混合粗粒度 (CG) 和原子 (AT) 模型，以及肽-蛋白质复合物的快速搜索和精修。与其他通常通过 CG 或 AT 力场模型来表示蛋白质空间上分离部分的混合模型不同，本方法通过 AT（统一原子）和 CG 模型同时表示蛋白质。蛋白质主链的相互作用基于统一原子力场进行描述，允许对蛋白质二级结构进行真实的表示。此外，所有其他键合相互作用的 AT 描述使蛋白质与真实的键合几何形状兼容。使用基于知识的势能在 CG 模型级别计算侧链与侧链和主链之间的非键相互作用。对几个测试蛋白质进行的无约束分子动力学模拟得到的轨迹与相应的实验结构基本一致。在对接肽-蛋白质复合物的精修中的应用导致了改进的复合物结构。在快速精修对接蛋白质-蛋白质复合物中也可以应用，但需要进一步优化力场参数。
