title: Testing beta-helix terminal coils stability by targeted substitutions with non-proteogenic amino acids: a molecular dynamics study.
abstract: The search for new building block templates useful for nanostructures design, targets protein motifs with a wide range of structures. Stabilizing these building blocks when extracted from their natural environment becomes a fundamental goal in order to successfully control their assembly. Targeted replacements of natural residues by conformationally constrained amino acids were shown to be a successful strategy to achieve such stabilization. In this work, the effect of replacing natural amino acids by non-proteogenic residues in a beta-helix building block has been evaluated using extensive molecular dynamics simulations. Here, we focus on systematic substitutions of valine residues present in beta-sheet segments of a beta-helical building block excised from Escherichia coli galactoside acetyltransferase, residues 131-165. Four different types of non-proteogenic amino acids have been considered for substitution: (i) one dehydroamino acid, (ii) two d-amino acids, (iii) one beta-amino acid and (iv) two alpha,alpha-dialkylamino acids. Our results indicate that the ability of non-proteogenic amino acids to stabilize small building block motifs is site-dependent. We conclude that if the replacement does not alter the energy balance between attractive non-covalent interactions and steric hindrance, synthetic residues are suitable candidates to nucleate beta-helix formation.
authors: Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, Barcelona E-08028, Spain. david.zanuy@upc.edu
authors: David
authors: D
authors: Zanuy
authors: Francisco
authors: F
authors: Rodríguez-Ropero
authors: Ruth
authors: R
authors: Nussinov
authors: Carlos
authors: C
authors: Alemán
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry; D020816:Amino Acid Motifs; D000596:Amino Acids / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D036103:Nanotechnology / Q000379:methods*; D043942:Nanotubes / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids; D009842:Oligopeptides; D010455:Peptides; D002244:Carbon; C015102:dehydroalanine; D000409:Alanine; D005998:Glycine