2024-03-28T22:35:18Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/193102016-02-16T06:08:37Zcom_10261_31com_10261_3col_10261_284
Use of constrained synthetic amino acids in β-Helix proteins for conformational control
Zanuy, David
Jiménez, Ana I.
Cativiela, Carlos
Nussinov, Ruth
Alemán, Carlos
7 pages, 4 figures, 1 table.
A highly constrained amino acid has been introduced in the turn region of a β-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 β-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 β-helix motif, which is the first requirement for further protein nanoengineering. A highly regular segment from a naturally occurring β-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 β-helix motif in isolated peptide segments.
2009-12-03T11:08:54Z
2009-12-03T11:08:54Z
2007-03
artículo
Journal of Physical Chemistry B 111(12): 3236-3242 (2007)
1520-6106
http://hdl.handle.net/10261/19310
10.1021/jp065025k
eng
http://dx.doi.org/10.1021/jp065025k
closedAccess
American Chemical Society