Recently, a potentially powerful strategy based on the of phage-display libraries has been presented to target tumors via homing peptides attached to nanoparticles. The Cys-Arg-Glu-Lys-Ala (CREKA) peptide sequence has been identified as a tumor-homing peptide that binds to clotted plasmas proteins present in tumor vessels and interstitium. The aim of this work consists of mapping the conformational profile of CREKA to identify the bioactive conformation. For this purpose, a conformational search procedure based on modified Simulated Annealing combined with Molecular Dynamics was applied to three systems that mimic the experimentally used conditions: (i) the free peptide; (ii) the peptide attached to a nanoparticle; and (iii) the peptide inserted in a phage display protein. In addition, the free peptide was simulated in an ionized aqueous solution environment, which mimics the ionic strength of the physiological medium. Accessible minima of all simulated systems reveal a multiple interaction pattern involving the ionized side chains of Arg, Glu and Lys, which induces a β-turn motif in the backbone observed in all simulated CREKA systems.
A very efficient computational procedure, which was previously developed to generate and relax atomistic models of linear and comb-like amorphous polymers, has been adapted to model the amorphous phase of polycyclic systems. The strategy, which is a based in a generation algorithm that eliminates the torsion strain and a simple Monte Carlo Metropolis method to relax the generated structures, has been used to predict the density of amorphous polythiophene by combining NVT and NPT simulations. The theoretical value is in the excellent agreement with the experimental one, the former being overestimated by only 3-5%. Next, the molecular conformation and the packing of the rings were studied in detail. Interestingly, the amorphous phase of polythiophene can be described as a packing of elongated molecular chains more or less aligned in the same direction, in which the thiophene rings close in the space but belonging to different chains tend to adopt approximate parallel or antiparallel displaced pi-stacked arrangements.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.