Exploring the energy landscape of a molecular engineered analog of a tumor-homing peptide.
Recently a new non-coded amino acid was designed as a replacement for Arg, to protect the tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) from proteases. This constrained Arg analog, denoted c(5)Arg, was engineered to also promote the stability of the CREKA bioactive conformation. The conformational profile of the CREKA analog obtained by replacing Arg by c(5)Arg has been extensively investigated in this work. Two molecular dynamics simulations-based strategies have been employed: a modified simulated annealing and replica exchange. Results obtained using both techniques show that the conformational features of the new analog fulfill the purpose of its design. The new CREKA analog not only preserves the main structural attributes found for the bioactive conformation of the parent peptide but also shows lower flexibility. Moreover, the conformational profile of the mutated peptide narrows towards the most stable structures previously observed for the parent CREKA peptide.
Departament d'Enginyeria Química, E. T. S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, Barcelona E-08028, Spain.
Guillem
G
Revilla-López
Juan
J
Torras
Ruth
R
Nussinov
Carlos
C
Alemán
David
D
Zanuy
D001120:Arginine / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics
D009842:Oligopeptides; C542438:cysteinyl-arginyl-glutamyl-lysyl-alanyl; D001120:Arginine
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