Identification of important residues in biochemical complexes is often a crucial step for many problems in molecular biology and biochemistry. A method is proposed to identify hotspots in biomolecular complexes based on a new metric, derived from networks representing molecular subunits (residues, bridging solvent molecules, ligands etc.) connected by interactions. A singular value decomposition of the weighted adjacency matrix is used to construct a scalar rank for each subunit that reflects its importance in the residue interaction network. This metric is called the singular value centrality. In addition, a new formalism is proposed to account for water-mediated interactions in the ranking of residues. Interactions for a residue network can be provided by various computational methods. In this work interactions are obtained from full quantum-mechanical calculations of protein–protein complexes using the fragment molecular orbital method. The ranking results are shown to be in good agreement with earlier computational and experimental studies. The developed method can be used to gain a deeper insight into the role of subunits in complex biomolecular systems.

中文翻译：

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直接和水介导的相互作用对具有多个子系统的生物分子复合物中热点鉴定的影响


鉴定生化复合物中的重要残基通常是分子生物学和生物化学中许多问题的关键步骤。提出了一种基于新度量物识别生物分子复合物中热点的方法，该度量来自代表通过相互作用连接的分子亚基（残基、桥接溶剂分子、配体等）的网络。加权邻接矩阵的奇异值分解用于为每个子基构建一个标量秩，以反映其在残基相互作用网络中的重要性。此指标称为奇异值中心性。此外，还提出了一种新的形式主义，以解释残基排序中水介导的相互作用。残基网络的交互可以通过各种计算方法提供。在这项工作中，使用片段分子轨道方法对蛋白质-蛋白质复合物进行全量子力学计算，获得相互作用。排名结果显示与早期的计算和实验研究非常一致。开发的方法可用于更深入地了解亚基在复杂生物分子系统中的作用。