Sowmya Gopichandran, Ranganathan Shoba
BMC Bioinformatics. 2015;16 Suppl 18(Suppl 18):S8. doi: 10.1186/1471-2105-16-S18-S8. Epub 2015 Dec 9.
Protein-protein interaction (PPI) is essential for molecular functions in biological cells. Investigation on protein interfaces of known complexes is an important step towards deciphering the driving forces of PPIs. Each PPI complex is specific, sensitive and selective to binding. Therefore, we have estimated the relative difference in percentage of polar residues between surface and the interface for each complex in a non-redundant heterodimer dataset of 278 complexes to understand the predominant forces driving binding.
Our analysis showed 60% of protein complexes with surface polarity greater than interface polarity (designated as class A). However, a considerable number of complexes (40%) have interface polarity greater than surface polarity, (designated as class B), with a significantly different p-value of 1.66E-45 from class A. Comprehensive analyses of protein complexes show that interface features such as interface area, interface polarity abundance, solvation free energy gain upon interface formation, binding energy and the percentage of interface charged residue abundance distinguish among class A and class B complexes, while electrostatic visualization maps also help differentiate interface classes among complexes.
Class A complexes are classical with abundant non-polar interactions at the interface; however class B complexes have abundant polar interactions at the interface, similar to protein surface characteristics. Five physicochemical interface features analyzed from the protein heterodimer dataset are discriminatory among the interface residue-level classes. These novel observations find application in developing residue-level models for protein-protein binding prediction, protein-protein docking studies and interface inhibitor design as drugs.
蛋白质-蛋白质相互作用（PPI）对于生物细胞中的分子功能至关重要。研究已知复合物的蛋白质界面是解读PPI驱动力的重要一步。每个PPI复合物在结合方面都是特异、敏感且具有选择性的。因此，我们估算了一个包含278个复合物的非冗余异源二聚体数据集中每个复合物表面和界面极性残基百分比的相对差异，以了解驱动结合的主要作用力。
我们的分析表明，约60%的蛋白质复合物表面极性大于界面极性（归类为A类）。然而，相当数量的复合物（约40%）界面极性大于表面极性（归类为B类），与A类的p值显著不同，为1.66E - 45。对蛋白质复合物的综合分析表明，诸如界面面积、界面极性丰度、界面形成时的溶剂化自由能增益、结合能以及界面带电残基丰度百分比等界面特征在A类和B类复合物之间存在差异，而静电可视化图也有助于区分复合物之间的界面类别。
A类复合物是典型的，在界面处具有丰富的非极性相互作用；然而B类复合物在界面处具有丰富的极性相互作用，类似于蛋白质表面特征。从蛋白质异源二聚体数据集中分析得到的五个物理化学界面特征在界面残基水平类别之间具有区分性。这些新发现可应用于开发用于蛋白质-蛋白质结合预测、蛋白质-蛋白质对接研究以及作为药物的界面抑制剂设计的残基水平模型。
