title: Use of constrained synthetic amino acids in beta-helix proteins for conformational control.
abstract: A highly constrained amino acid has been introduced in the turn region of a beta-helix to increase the conformational stability of the native fold for nanotechnological purposes. The influence of this specific amino acid replacement in the final organization of beta-helix motifs has been evaluated by combining ab initio first-principles calculations on model systems and molecular dynamics simulations of entire peptide segments. The former methodology, which has been applied to a sequence containing three amino acids, has been used to develop adjusted templates. Calculations indicated that 1-amino-2,2-diphenylcyclopropanecarboxylic acid, a constrained cyclopropane analogue of phenylalanine, exhibits a strong tendency to form and promote folded conformations. On the other hand, molecular dynamics simulations are employed to probe the ability of such a synthetic amino acid to enhance the conformational stability of the beta-helix motif, which is the first requirement for further protein nanoengineering. A highly regular segment from a naturally occurring beta-helix protein was selected as a potential nanoconstruct module. Simulations of wild type and mutated segments revealed that the ability of the phenylalanine analogue to nucleate turn conformations enhances the conformational stability of the beta-helix motif in isolated peptide segments.
authors: Departament d'Enginyeria Química, ETSEIB, Universitat Politècnica de Catalunya, Diagonal 647, 08028 Barcelona, Spain.
authors: David
authors: D
authors: Zanuy
authors: Ana I
authors: AI
authors: Jiménez
authors: Carlos
authors: C
authors: Cativiela
authors: Ruth
authors: R
authors: Nussinov
authors: Carlos
authors: C
authors: Alemán
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D008958:Models, Molecular; D009154:Mutation; D016011:Normal Distribution; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D007202:Indicators and Reagents; D011506:Proteins