{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:01:07Z","timestamp":1783598467408,"version":"3.55.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Most biological processes are mediated by the protein\u2013protein interactions. Determination of the protein\u2013protein structures and insight into their interactions are vital to understand the mechanisms of protein functions. Currently, compared with the isolated protein structures, only a small fraction of protein\u2013protein structures are experimentally solved. Therefore, the computational docking methods play an increasing role in predicting the structures and interactions of protein\u2013protein complexes. The scoring function of protein\u2013protein interactions is the key responsible for the accuracy of the computational docking. Previous scoring functions were mostly developed by optimizing the binding affinity which determines the stability of the protein\u2013protein complex, but they are often lack of the consideration of specificity which determines the discrimination of native protein\u2013protein complex against competitive ones.<\/jats:p><jats:p>Results: We developed a scoring function (named as SPA-PP, specificity and affinity of the protein\u2013protein interactions) by incorporating both the specificity and affinity into the optimization strategy. The testing results and comparisons with other scoring functions show that SPA-PP performs remarkably on both predictions of binding pose and binding affinity. Thus, SPA-PP is a promising quantification of protein\u2013protein interactions, which can be implemented into the protein docking tools and applied for the predictions of protein\u2013protein structure and affinity.<\/jats:p><jats:p>Availability: The algorithm is implemented in C language, and the code can be downloaded from http:\/\/dl.dropbox.com\/u\/1865642\/Optimization.cpp.<\/jats:p><jats:p>Contact: \u00a0jin.wang.1@stonybrook.edu<\/jats:p><jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt121","type":"journal-article","created":{"date-parts":[[2013,3,9]],"date-time":"2013-03-09T01:41:26Z","timestamp":1362793286000},"page":"1127-1133","source":"Crossref","is-referenced-by-count":30,"title":["Specificity and affinity quantification of protein\u2013protein interactions"],"prefix":"10.1093","volume":"29","author":[{"given":"Zhiqiang","family":"Yan","sequence":"first","affiliation":[{"name":"1 Department of Chemistry and Physics, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA, 2College of Computer Science and Technology, Jilin University, Changchun, Jilin 130012, China and 3State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyong","family":"Guo","sequence":"additional","affiliation":[{"name":"1 Department of Chemistry and Physics, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA, 2College of Computer Science and Technology, Jilin University, Changchun, Jilin 130012, China and 3State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hu","sequence":"additional","affiliation":[{"name":"1 Department of Chemistry and Physics, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA, 2College of Computer Science and Technology, Jilin University, Changchun, Jilin 130012, China and 3State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"1 Department of Chemistry and Physics, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA, 2College of Computer Science and Technology, Jilin University, Changchun, Jilin 130012, China and 3State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China"},{"name":"1 Department of Chemistry and Physics, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA, 2College of Computer Science and Technology, Jilin University, Changchun, Jilin 130012, China and 3State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,3,7]]},"reference":[{"key":"2023012810315537100_btt121-B1","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gkm993","article-title":"Data growth and its impact on the scop database: new developments","volume":"36","author":"Andreeva","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023012810315537100_btt121-B2","doi-asserted-by":"crossref","first-page":"12724","DOI":"10.1073\/pnas.0506124102","article-title":"Specificity versus stability in computational protein design","volume":"102","author":"Bolon","year":"2005","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012810315537100_btt121-B3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/prot.340210302","article-title":"Funnels, pathways, and the energy landscape of protein folding: a synthesis","volume":"21","author":"Bryngelson","year":"1995","journal-title":"Proteins"},{"key":"2023012810315537100_btt121-B4","doi-asserted-by":"crossref","first-page":"e22477","DOI":"10.1371\/journal.pone.0022477","article-title":"Benchmarking and analysis of protein docking performance in rosetta v3","volume":"6","author":"Chaudhury","year":"2011","journal-title":"2. 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Physiol."},{"key":"2023012810315537100_btt121-B37","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1002\/prot.24144","article-title":"Characterizing the morphology of protein binding patches","volume":"80","author":"Malod-Dognin","year":"2012","journal-title":"Proteins"},{"key":"2023012810315537100_btt121-B38","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1002\/pro.5560061011","article-title":"Ligand binding to proteins: the binding landscape model","volume":"6","author":"Miller","year":"1997","journal-title":"Protein Sci."},{"key":"2023012810315537100_btt121-B39","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1093\/bioinformatics\/btr513","article-title":"Protein\u2013protein binding affinity prediction on a diverse set of structures","volume":"27","author":"Moal","year":"2011","journal-title":"Bioinformatics"},{"key":"2023012810315537100_btt121-B40","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/jcc.21276","article-title":"Protein\u2013protein docking dealing with the unknown","volume":"31","author":"Moreira","year":"2010","journal-title":"J. Comput. Chem."},{"key":"2023012810315537100_btt121-B41","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1021\/jm980536j","article-title":"A general and fast scoring function for protein-ligand interactions: a simplified potential approach","volume":"42","author":"Muegge","year":"1999","journal-title":"J. Med. Chem."},{"key":"2023012810315537100_btt121-B42","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1093\/bioinformatics\/btl115","article-title":"Gbpm: Grid-based pharmacophore model: concept and application studies to protein\u2013protein recognition","volume":"22","author":"Ortuso","year":"2006","journal-title":"Bioinformatics"},{"key":"2023012810315537100_btt121-B43","doi-asserted-by":"crossref","first-page":"8945","DOI":"10.1073\/pnas.93.17.8945","article-title":"Unraveling principles of lead discovery: from unfrustrated energy landscapes to novel molecular anchors","volume":"93","author":"Rejto","year":"1996","journal-title":"Proc. Natl Acad. Sci. 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USA"},{"key":"2023012810315537100_btt121-B47","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0022-2836(05)80269-4","article-title":"Calculation of conformational ensembles from potentials of mena force: an approach to the knowledge-based prediction of local structures in globular proteins","volume":"213","author":"Sippl","year":"1990","journal-title":"J. Mol. Biol."},{"key":"2023012810315537100_btt121-B48","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jsb.2008.06.002","article-title":"The future is hybrid","volume":"163","author":"Steven","year":"2008","journal-title":"J. Struct. Biol."},{"key":"2023012810315537100_btt121-B49","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1002\/pro.257","article-title":"Quantitative prediction of protein\u2013protein binding affinity with a potential of mean force considering volume correction","volume":"18","author":"Su","year":"2009","journal-title":"Protein Sci."},{"key":"2023012810315537100_btt121-B50","doi-asserted-by":"crossref","first-page":"11628","DOI":"10.1073\/pnas.93.21.11628","article-title":"An iterative method for extracting energy-like quantities from protein structures","volume":"93","author":"Thomas","year":"1996","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012810315537100_btt121-B51","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1006\/jmbi.1996.0175","article-title":"Statistical potentials extracted from protein structures: how accurate are they?","volume":"257","author":"Thomas","year":"1996","journal-title":"J. Mol. Biol."},{"key":"2023012810315537100_btt121-B52","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1110\/ps.8.6.1181","article-title":"Folding funnels, binding funnels, and protein function","volume":"8","author":"Tsai","year":"1999","journal-title":"Protein Sci."},{"key":"2023012810315537100_btt121-B53","doi-asserted-by":"crossref","first-page":"188101","DOI":"10.1103\/PhysRevLett.90.188101","article-title":"Energy landscape theory, funnels, specificity, and optimal criterion of biomolecular binding","volume":"90","author":"Wang","year":"2003","journal-title":"Phys. Rev. Lett."},{"key":"2023012810315537100_btt121-B54","doi-asserted-by":"crossref","first-page":"198101","DOI":"10.1103\/PhysRevLett.99.198101","article-title":"Quantifying intrinsic specificity: a potential complement to affinity in drug screening","volume":"99","author":"Wang","year":"2007","journal-title":"Phys. Rev. Lett."},{"key":"2023012810315537100_btt121-B55","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/srep00309","article-title":"Specificity quantification of biomolecular recognition and its implication for drug discovery","volume":"2","author":"Yan","year":"2012","journal-title":"Sci. Rep."},{"key":"2023012810315537100_btt121-B56","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.sbi.2010.02.001","article-title":"Accounting for conformational changes during protein-protein docking","volume":"20","author":"Zacharias","year":"2010","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2023012810315537100_btt121-B57","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1021\/jm049314d","article-title":"A knowledge-based energy function for protein-ligand, protein-protein, and protein-DNA complexes","volume":"48","author":"Zhang","year":"2005","journal-title":"J. Med. 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