title: Protein-Protein Interaction for the De Novo Design of Cyclin-Dependent Kinase Peptide Inhibitors.
abstract: The homology of the inhibitor binding site regions on the surface of cyclin-dependent kinases (CDKs) makes actual CDK inhibitors unable to bind specifically to their molecular targets. Most of them are ATP competitive inhibitors with low specificity that also affect the phosphorylation mechanisms of other nontarget kinases giving rise to harmful side effects. So, the search of specific and potent inhibitors able to bind to the desired CDK target is still a pending issue. Structure based drug design minimized the erroneous binding and increased the affinity of the inhibitor interaction. In the case of CDKs their activation and regulation mechanisms mainly depend on protein-protein interactions (PPIs). The design of drugs targeting these PPIs makes feasible and promising towards the discovery of new and specific CDK inhibitors. Development of peptide inhibitors for a target protein is an emerging approach in computer aided drug designing. This chapter describes in detail methodology for use of the VitAL-Viterbi algorithm for de novo peptide design of CDK2 inhibitors.
authors.affiliation: Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Science Block, 4th Floor, Karaikudi, 630003, Tamil Nadu, India.
authors.forename: Karthiga
authors.initials: K
authors.lastname: Arumugasamy
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Tripathi
authors.forename: Poonam
authors.initials: P
authors.lastname: Singh
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry; D001665:Binding Sites; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000737:chemistry; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D030562:Databases, Protein; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015233:Models, Statistical; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D012984:Software; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D010455:Peptides; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases