title: Molecular dynamics simulations and statistical coupling analysis reveal functional coevolution network of oncogenic mutations in the CDKN2A-CDK6 complex.
abstract: Coevolution between proteins is crucial for understanding protein-protein interaction. Simultaneous changes allow a protein complex to maintain its overall structural-functional integrity. In this study, we combined statistical coupling analysis (SCA) and molecular dynamics simulations on the CDK6-CDKN2A protein complex to evaluate coevolution between proteins. We reconstructed an inter-protein residue coevolution network, consisting of 37 residues and 37 interactions. It shows that most of the coevolved residue pairs are spatially proximal. When the mutations happened, the stable local structures were broken up and thus the protein interaction was decreased or inhibited, with a following increased risk of melanoma. The identification of inter-protein coevolved residues in the CDK6-CDKN2A complex can be helpful for designing protein engineering experiments.
authors.affiliation: Yantai Yuhuangding Hospital, Yantai, Shandong Province 264000, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Wang
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Wang
authors.forename: Jingfei
authors.initials: J
authors.lastname: Huang
mesh_terms: D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000737:chemistry* / Q000235:genetics*; D015195:Drug Design; D019143:Evolution, Molecular; D019942:Genes, p16; D006801:Humans; D008545:Melanoma / Q000209:etiology / Q000235:genetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics; D009154:Mutation; D009857:Oncogenes; D054730:Protein Interaction Domains and Motifs; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D046912:Multiprotein Complexes; D050505:Mutant Proteins; D047428:Protein Kinase Inhibitors; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6