title: Co-Occurring Atomic Contacts for the Characterization of Protein Binding Hot Spots.
abstract: A binding hot spot is a small area at a protein-protein interface that can make significant contribution to binding free energy. This work investigates the substantial contribution made by some special co-occurring atomic contacts at a binding hot spot. A co-occurring atomic contact is a pair of atomic contacts that are close to each other with no more than three covalent-bond steps. We found that two kinds of co-occurring atomic contacts can play an important part in the accurate prediction of binding hot spot residues. One is the co-occurrence of two nearby hydrogen bonds. For example, mutations of any residue in a hydrogen bond network consisting of multiple co-occurring hydrogen bonds could disrupt the interaction considerably. The other kind of co-occurring atomic contact is the co-occurrence of a hydrophobic carbon contact and a contact between a hydrophobic carbon atom and a π ring. In fact, this co-occurrence signifies the collective effect of hydrophobic contacts. We also found that the B-factor measurements of several specific groups of amino acids are useful for the prediction of hot spots. Taking the B-factor, individual atomic contacts and the co-occurring contacts as features, we developed a new prediction method and thoroughly assessed its performance via cross-validation and independent dataset test. The results show that our method achieves higher prediction performance than well-known methods such as Robetta, FoldX and Hotpoint. We conclude that these contact descriptors, in particular the novel co-occurring atomic contacts, can be used to facilitate accurate and interpretable characterization of protein binding hot spots.
authors.affiliation: Advanced Analytics Institute, University of Technology Sydney, Broadway, NSW 2007, Australia.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Advanced Analytics Institute, University of Technology Sydney, Broadway, NSW 2007, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Monash University, Melbourne, VIC 3800, Australia.|Centre for Research in Intelligent Systems, Faculty of Information Technology, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Song
authors.affiliation: Advanced Analytics Institute and Centre for Health Technologies, University of Technology Sydney, Broadway, NSW 2007, Australia.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Li
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D011506:Proteins