Investigation of atomic level patterns in protein--small ligand interactions.
Investigation of atomic level patterns in protein--small ligand interactions.
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DOI：
10.1371/journal.pone.0004473
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Kurgan L
中科院分区：
文献类型：
--
作者：
Chen K;Kurgan L
形状互补和非共价相互作用被认为是驱动蛋白质-配体相互作用的因素。到目前为止，系统地研究了蛋白质-蛋白质、蛋白质-DNA和蛋白质-RNA的相互作用，这与与小配体的相互作用形成了对比。我们使用2,320个复合体的综合数据集研究了共价键和非共价键在蛋白质-小配体相互作用中的作用。我们发现，对于不同的配体类型，蛋白质-配体相互作用受不同作用力的支配，即蛋白质-有机化合物相互作用受氢键、van der Waals键和共价键支配；蛋白质-金属离子相互作用受静电力、氢键和配位键支配；蛋白质-阴离子相互作用由静电作用力、氢键和van der Waals相互作用建立；蛋白质-无机簇合物相互作用由配位键驱动。我们提取了几个关于这些相互作用的频繁出现的原子级模式。例如，所研究的73%的共价键只有三种形式，即半胱氨酸的硫醇与配体的碳或硫原子之间以及赖氨酸的氮与配体的碳原子之间形成的键。配位键也发现了类似的模式。67%的蛋白质-有机化合物络合物中存在氢键，其中66%的氢键是在蛋白质残基的NH-基团与配体的氧原子之间形成的。我们量化了特定交互类型的相对丰富性，并讨论了它们的特征。提取的蛋白质-有机化合物模式被证明是对结合位点预测的几何方法的补充和改进。我们发现，对于给定的配体类型和作用力类型，大多数蛋白质-配体相互作用都是重复的，可以用几个简单的原子水平模式来概括。我们总结和分析了10种常见的相互作用模式，覆盖了所有考虑的络合物的56%，并展示了涉及与有机化合物相互作用的模式的实际应用。
Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes. We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites. We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.
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