title: Prediction of peptides binding to the PKA RIIalpha subunit using a hierarchical strategy.
abstract: BACKGROUND
  Favorable interaction between the regulatory subunit of the cAMP-dependent protein kinase (PKA) and a peptide in A-kinase anchoring proteins (AKAPs) is critical for translocating PKA to the subcellular sites where the enzyme phosphorylates its substrates. It is very hard to identify AKAPs peptides binding to PKA due to the high sequence diversity of AKAPs.
  
  
  RESULTS
  We propose a hierarchical and efficient approach, which combines molecular dynamics (MD) simulations, free energy calculations, virtual mutagenesis (VM) and bioinformatics analyses, to predict peptides binding to the PKA RIIα regulatory subunit in the human proteome systematically. Our approach successfully retrieved 15 out of 18 documented RIIα-binding peptides. Literature curation supported that many newly predicted peptides might be true AKAPs. Here, we present the first systematic search for AKAP peptides in the human proteome, which is useful to further experimental identification of AKAPs and functional analysis of their biological roles.
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, PR China. tingjunhou@hotmail.com
authors.forename: Tingjun
authors.initials: T
authors.lastname: Hou
authors.forename: Youyong
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D054758:A Kinase Anchor Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D000595:Amino Acid Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021122:Protein Subunits / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
chemical_list: D054758:A Kinase Anchor Proteins; D010455:Peptides; D021122:Protein Subunits; D017868:Cyclic AMP-Dependent Protein Kinases