title: Folding and binding energy of a calmodulin-binding cell antiproliferative peptide.
abstract: We carry out a computational study of a calmodulin-binding peptide shown to be effective in reducing cell proliferation. We find several folded states for two short variants of different length of the peptide and determine the location of the binding site on calmodulin, the binding free energy for the different conformers and structural details that play a role in optimal binding. Binding to a hydrophobic pocket in calmodulin occurs via an anchoring phenylalanine residue of the natively disordered peptide, and is enhanced when a neighbouring hydrophobic residue acts as a co-anchor. The shorter sequence possesses better binding to calmodulin, which is encouraging in terms of the development of non-peptide analogues as therapeutic agents.
authors: Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada.
authors: Ahmad M
authors: AM
authors: Almudallal
authors: Department of Physics and Physical Oceanography, Memorial University of Newfoundland, St. John's, NL A1B 3X7, Canada. Electronic address: saika@mun.ca.
authors: Ivan
authors: I
authors: Saika-Voivod
authors: Soricimed Biopharma Inc., Sackville, NB E4L 4H2, Canada.
authors: John M
authors: JM
authors: Stewart
mesh_terms: D020816:Amino Acid Motifs; D000970:Antineoplastic Agents / Q000737:chemistry*; D001665:Binding Sites; D002147:Calmodulin / Q000737:chemistry*; D002148:Calmodulin-Binding Proteins / Q000737:chemistry*; D015195:Drug Design; D057166:High-Throughput Screening Assays; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014584:User-Computer Interface
chemical_list: D000970:Antineoplastic Agents; D002147:Calmodulin; D002148:Calmodulin-Binding Proteins; D008024:Ligands; D010455:Peptides; D010649:Phenylalanine
keywords: Docking; Drug design; Molecular dynamics simulation; Peptide binding; Peptide modelling