title: Integrating the intrinsic conformational preferences of noncoded α-amino acids modified at the peptide bond into the noncoded amino acids database.
abstract: Recently, we reported a database (Noncoded Amino acids Database; http://recerca.upc.edu/imem/index.htm) that was built to compile information about the intrinsic conformational preferences of nonproteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, the experimentally established conformational propensities, and applications (Revilla-López et al., J Phys Chem B 2010;114:7413-7422). The database initially contained the information available for α-tetrasubstituted α-amino acids. In this work, we extend NCAD to three families of compounds, which can be used to engineer peptides and proteins incorporating modifications at the--NHCO--peptide bond. Such families are: N-substituted α-amino acids, thio-α-amino acids, and diamines and diacids used to build retropeptides. The conformational preferences of these compounds have been analyzed and described based on the information captured in the database. In addition, we provide an example of the utility of the database and of the compounds it compiles in protein and peptide engineering. Specifically, the symmetry of a sequence engineered to stabilize the 3(10)-helix with respect to the α-helix has been broken without perturbing significantly the secondary structure through targeted replacements using the information contained in the database.
authors.affiliation: Departament d'Enginyeria Química, ETS d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, 08028 Barcelona, Spain.
authors.forename: Guillem
authors.initials: G
authors.lastname: Revilla-López
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodríguez-Ropero
authors.forename: David
authors.initials: D
authors.lastname: Curcó
authors.forename: Juan
authors.initials: J
authors.lastname: Torras
authors.forename: M
authors.initials: M
authors.lastname: Isabel Calaza
authors.forename: David
authors.initials: D
authors.lastname: Zanuy
authors.forename: Ana I
authors.initials: AI
authors.lastname: Jiménez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Carlos
authors.initials: C
authors.lastname: Alemán
mesh_terms: D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry*; D016208:Databases, Factual; D003959:Diamines / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000596:Amino Acids; D003959:Diamines; D010455:Peptides; D013438:Sulfhydryl Compounds