title: Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl-like molecules binding.
abstract: BACKGROUND
  Protein-Protein Interactions (PPIs) are key for many cellular processes. The characterization of PPI interfaces and the prediction of putative ligand binding sites and hot spot residues are essential to design efficient small-molecule modulators of PPI. Terphenyl and its derivatives are small organic molecules known to mimic one face of protein-binding alpha-helical peptides. In this work we focus on several PPIs mediated by alpha-helical peptides.
  
  
  METHODS
  We performed computational sequence- and structure-based analyses in order to evaluate several key physicochemical and surface properties of proteins known to interact with alpha-helical peptides and/or terphenyl and its derivatives.
  
  
  RESULTS
  Sequence-based analysis revealed low sequence identity between some of the analyzed proteins binding alpha-helical peptides. Structure-based analysis was performed to calculate the volume, the fractal dimension roughness and the hydrophobicity of the binding regions. Besides the overall hydrophobic character of the binding pockets, some specificities were detected. We showed that the hydrophobicity is not uniformly distributed in different alpha-helix binding pockets that can help to identify key hydrophobic hot spots.
  
  
  CONCLUSIONS
  The presence of hydrophobic cavities at the protein surface with a more complex shape than the entire protein surface seems to be an important property related to the ability of proteins to bind alpha-helical peptides and low molecular weight mimetics. Characterization of similarities and specificities of PPI binding sites can be helpful for further development of small molecules targeting alpha-helix binding proteins.
authors.affiliation: Department of Biology and Chemistry, West University of Timisoara, 16 Pestalozzi, Timisoara 300115, Romania.
authors.forename: Adriana
authors.initials: A
authors.lastname: Isvoran
authors.forename: Dana
authors.initials: D
authors.lastname: Craciun
authors.forename: Virginie
authors.initials: V
authors.lastname: Martiny
authors.forename: Olivier
authors.initials: O
authors.lastname: Sperandio
authors.forename: Maria A
authors.initials: MA
authors.lastname: Miteva
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002147:Calmodulin / Q000737:chemistry; D018797:Cell Cycle Proteins / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry; D016415:Sequence Alignment; D013499:Surface Properties; D013730:Terphenyl Compounds / Q000737:chemistry*; D019209:Troponin C / Q000737:chemistry; D051020:bcl-X Protein / Q000737:chemistry
chemical_list: C494811:BCL2L1 protein, human; C472752:CETN2 protein, human; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D018797:Cell Cycle Proteins; D013730:Terphenyl Compounds; D019209:Troponin C; D051020:bcl-X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2