RESUMO
Fluorescence spectroscopy and Molecular Dynamics results show that cholesterol reduces water along the chains in ether lipids by changing the water distribution pattern between tightly and loosely bound water molecules. Water distribution was followed by emission spectra and generalized polarization of 6-dodecanoyl-2-dimethyl aminonaphthalene (Laurdan) inserted in 1,2-dimiristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-di-O-tetradecyl-sn-glycero-3-phosphocholine (14: 0 Diether PC) membranes. Molecular Dynamics simulations indicate that the action of cholesterol could be different in ether PC in comparison to ester PC. In addition, Cholesterol seems to act "per se" as an additional hydration center in ether lipids. Regardless of the phase state, cholesterol both in DMPC and 14:0 Diether PC vesicles, changed the distribution of water molecules decreasing the dipole relaxation of the lipid interphase generating an increase in the non-relaxable population. Above 10% Cholesterol/14:0 Diether PC ratio vesicles' interphase present an environment around Laurdan molecules similar to that corresponding to ester PC.
Assuntos
Colesterol/química , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Espectrometria de Fluorescência , Relação Estrutura-AtividadeRESUMO
We carry out a time-averaged contact matrix study to reveal the existence of protein backbone hydrogen bonds (BHBs) whose net persistence in time differs markedly form their corresponding PDB-reported state. We term such interactions as "chameleonic" BHBs, CBHBs, precisely to account for their tendency to change the structural prescription of the PDB for the opposite bonding propensity in solution. We also find a significant enrichment of protein binding sites in CBHBs, relate them to local water exposure and analyze their behavior as ligand/drug targets. Thus, the dynamic analysis of hydrogen bond propensity might lay the foundations for new tools of interest in protein binding-site prediction and in lead optimization for drug design.