Protein-DNA docking with a coarse-grained force field.
Protein-DNA docking with a coarse-grained force field.
复制标题
DOI：
10.1186/1471-2105-13-228
复制
发表时间：
2012-09-11
影响因子：
3
通讯作者：
Zacharias M
中科院分区：
文献类型：
--
作者：
Setny P;Bahadur RP;Zacharias M
蛋白质-DNA 相互作用对于许多细胞过程很重要，但是仍然缺乏大部分已知和推定复合物的结构知识。计算对接方法旨在根据其组成部分的详细结构来预测复杂架构。它们正在成为大分子组装领域中越来越重要的工具，补充了要求特别高的蛋白质核酸 X 射线晶体学，并为来自快速发展的方法（例如冷冻电子显微镜）的低分辨率数据的精炼和整合提供了手段。我们提出了一种适合蛋白质-DNA 对接的新粗粒度力场。力场是先前开发的蛋白质-RNA 和蛋白质-蛋白质相互作用参数集的扩展。对接基于结合伙伴的平移和定向自由度的势能最小化。它允许快速有效地系统搜索类似原生的复杂几何形状，而无需任何有关结合位点位置的先验知识。我们发现力场对于束缚对接给出了非常好的结果。在未绑定对接的情况下，预测的质量会有所不同，具体取决于与绑定几何形状的结构偏差程度。我们分析了特定蛋白质-DNA 相互作用对力场性能的作用，包括复杂结构预测和实验结合亲和力的再现。我们发现这种直接、特异性的相互作用仅部分有助于蛋白质-DNA 识别，表明形状互补性和序列依赖性 DNA 内能的重要作用，符合间接蛋白质-DNA 读出机制的概念。
Protein-DNA interactions are important for many cellular processes, however structural knowledge for a large fraction of known and putative complexes is still lacking. Computational docking methods aim at the prediction of complex architecture given detailed structures of its constituents. They are becoming an increasingly important tool in the field of macromolecular assemblies, complementing particularly demanding protein-nucleic acids X ray crystallography and providing means for the refinement and integration of low resolution data coming from rapidly advancing methods such as cryoelectron microscopy. We present a new coarse-grained force field suitable for protein-DNA docking. The force field is an extension of previously developed parameter sets for protein-RNA and protein-protein interactions. The docking is based on potential energy minimization in translational and orientational degrees of freedom of the binding partners. It allows for fast and efficient systematic search for native-like complex geometry without any prior knowledge regarding binding site location. We find that the force field gives very good results for bound docking. The quality of predictions in the case of unbound docking varies, depending on the level of structural deviation from bound geometries. We analyze the role of specific protein-DNA interactions on force field performance, both with respect to complex structure prediction, and the reproduction of experimental binding affinities. We find that such direct, specific interactions only partially contribute to protein-DNA recognition, indicating an important role of shape complementarity and sequence-dependent DNA internal energy, in line with the concept of indirect protein-DNA readout mechanism.
登录
查看更多内容
影响因子：
2.9
作者：
Janin, Joel
通讯作者：
Janin, Joel
影响因子：
5.6
作者：
Holbrook, JA;Tsodikov, OV;Record, MT
通讯作者：
Record, MT
影响因子：
4.8
作者：
CoskunAri, FF;Hill, TM
通讯作者：
Hill, TM
影响因子：
2.9
作者：
HYRE, DE;SPICER, LD
通讯作者：
SPICER, LD
影响因子：
5.6
作者：
Dragan, AI;Klass, J;Privalov, PL
通讯作者：
Privalov, PL