2015 |
Celis-Barros, C; Saavedra-Rivas, L; Salgado, J C; Cassels, B K; Zapata-Torres, G Molecular Dynamics Simulation of Halogen Bonding Mimics Experimental Data for Cathepsin L Inhibition Artículo de revista Journal of Computer-Aided Molecular Design, 29 (1), pp. 37-46, 2015, ISSN: 0920-654x. Resumen | Enlaces | BibTeX | Etiquetas: atherosclerosis, bonding, bromine cathepsin cathepsins, cysteine design, discovery, disease, drug force-field, halogen halogenated inhibitors, interactions, l, md optimization, protein-ligand sigma-hole, simulation @article{RN244, title = {Molecular Dynamics Simulation of Halogen Bonding Mimics Experimental Data for Cathepsin L Inhibition}, author = { C. Celis-Barros and L. Saavedra-Rivas and J.C. Salgado and B.K. Cassels and G. Zapata-Torres}, url = {/brokenurl#<Go to ISI>://WOS:000346913200004}, doi = {10.1007/s10822-014-9802-7}, issn = {0920-654x}, year = {2015}, date = {2015-01-01}, journal = {Journal of Computer-Aided Molecular Design}, volume = {29}, number = {1}, pages = {37-46}, abstract = {A MD simulation protocol was developed to model halogen bonding in protein-ligand complexes by inclusion of a charged extra point to represent the anisotropic distribution of charge on the halogen atom. This protocol was then used to simulate the interactions of cathepsin L with a series of halogenated and non-halogenated inhibitors. Our results show that chloro, bromo and iodo derivatives have progressively narrower distributions of calculated geometries, which reflects the order of affinity I > Br > Cl, in agreement with the IC50 values. Graphs for the Cl, Br and I analogs show stable interactions between the halogen atom and the Gly61 carbonyl oxygen of the enzyme. The halogen-oxygen distance is close to or less than the sum of the van der Waals radii; the C-X center dot center dot center dot O angle is about 170A degrees; and the X center dot center dot center dot O=C angle approaches 120A degrees, as expected for halogen bond formation. In the case of the iodo-substituted analogs, these effects are enhanced by introduction of a fluorine atom on the inhibitors' halogen-bonding phenyl ring, indicating that the electron withdrawing group enlarges the sigma-hole, resulting in improved halogen bonding properties.}, keywords = {atherosclerosis, bonding, bromine cathepsin cathepsins, cysteine design, discovery, disease, drug force-field, halogen halogenated inhibitors, interactions, l, md optimization, protein-ligand sigma-hole, simulation}, pubstate = {published}, tppubtype = {article} } A MD simulation protocol was developed to model halogen bonding in protein-ligand complexes by inclusion of a charged extra point to represent the anisotropic distribution of charge on the halogen atom. This protocol was then used to simulate the interactions of cathepsin L with a series of halogenated and non-halogenated inhibitors. Our results show that chloro, bromo and iodo derivatives have progressively narrower distributions of calculated geometries, which reflects the order of affinity I > Br > Cl, in agreement with the IC50 values. Graphs for the Cl, Br and I analogs show stable interactions between the halogen atom and the Gly61 carbonyl oxygen of the enzyme. The halogen-oxygen distance is close to or less than the sum of the van der Waals radii; the C-X center dot center dot center dot O angle is about 170A degrees; and the X center dot center dot center dot O=C angle approaches 120A degrees, as expected for halogen bond formation. In the case of the iodo-substituted analogs, these effects are enhanced by introduction of a fluorine atom on the inhibitors' halogen-bonding phenyl ring, indicating that the electron withdrawing group enlarges the sigma-hole, resulting in improved halogen bonding properties. |
2013 |
Bahamonde-Padilla, V E; Espinoza, J; Weiss-Lopez, B; Cascales, J J L; Montecinos, R; Araya-Maturana, R Effect of Lithium on the Properties of a Liquid Crystal Formed by Sodium Dodecylsulphate and Decanol in Aqueous Solution Artículo de revista Journal of Chemical Physics, 139 (1), 2013, ISSN: 0021-9606. Resumen | Enlaces | BibTeX | Etiquetas: ewald, membrane, mesh micelle, molecular-dynamics number, particle phase, simulation, state systems, water @article{RN155, title = {Effect of Lithium on the Properties of a Liquid Crystal Formed by Sodium Dodecylsulphate and Decanol in Aqueous Solution}, author = { V.E. Bahamonde-Padilla and J. Espinoza and B. Weiss-Lopez and J.J.L. Cascales and R. Montecinos and R. Araya-Maturana}, url = {/brokenurl#<Go to ISI>://WOS:000321716400032}, doi = {10.1063/1.4811678}, issn = {0021-9606}, year = {2013}, date = {2013-01-01}, journal = {Journal of Chemical Physics}, volume = {139}, number = {1}, publisher = {2013 AIP Publishing LLC.}, abstract = {Understanding the molecular interactions that rule the physicochemical properties of molecular assemblies is of particular interest when trying to explain the behavior of much more complicated systems, such as the cell membranes. This work was devoted to study a discotic nematic lyotropic liquid crystal, formed by sodium dodecylsulphate (3% SDS-d(25)) and decanol (20% DeOH-alpha-d(2)), dissolved in aqueous solutions (0.1% D2O) of Na2SO4 or Li2SO4. The average size of the aggregates was estimated using fluorescence quenching experiments, and their dynamics were studied by measuring the H-2-NMR quadrupole splitting (Delta nu(Q)) and the longitudinal relaxation times (T-1) of the deuterated species. To provide an atomic insight into these assemblies, molecular dynamics simulations of the systems were carried out with atomic detail. As a previous step in this study, a reparameterization of the standard GROMOS 87 force field was required to perform the equilibrated simulations and to prevent instabilities emerging during the simulations. Finally, an excellent agreement between simulation and experimental data was obtained. In addition, variations in the long range electrostatic interactions at the aggregate/solution interface, the orientation and the re-orientational relaxation time of the water dipole, the translational diffusion coefficient of sodium ions, and the amphiphile-counterion coordination associated with the presence of Li+ in the solution were other keywords aspects investigated to explain the variation in the quadrupole splittings (Delta nu(Q)) in the presence of lithium in solution.}, keywords = {ewald, membrane, mesh micelle, molecular-dynamics number, particle phase, simulation, state systems, water}, pubstate = {published}, tppubtype = {article} } Understanding the molecular interactions that rule the physicochemical properties of molecular assemblies is of particular interest when trying to explain the behavior of much more complicated systems, such as the cell membranes. This work was devoted to study a discotic nematic lyotropic liquid crystal, formed by sodium dodecylsulphate (3% SDS-d(25)) and decanol (20% DeOH-alpha-d(2)), dissolved in aqueous solutions (0.1% D2O) of Na2SO4 or Li2SO4. The average size of the aggregates was estimated using fluorescence quenching experiments, and their dynamics were studied by measuring the H-2-NMR quadrupole splitting (Delta nu(Q)) and the longitudinal relaxation times (T-1) of the deuterated species. To provide an atomic insight into these assemblies, molecular dynamics simulations of the systems were carried out with atomic detail. As a previous step in this study, a reparameterization of the standard GROMOS 87 force field was required to perform the equilibrated simulations and to prevent instabilities emerging during the simulations. Finally, an excellent agreement between simulation and experimental data was obtained. In addition, variations in the long range electrostatic interactions at the aggregate/solution interface, the orientation and the re-orientational relaxation time of the water dipole, the translational diffusion coefficient of sodium ions, and the amphiphile-counterion coordination associated with the presence of Li+ in the solution were other keywords aspects investigated to explain the variation in the quadrupole splittings (Delta nu(Q)) in the presence of lithium in solution. |
2015 |
Molecular Dynamics Simulation of Halogen Bonding Mimics Experimental Data for Cathepsin L Inhibition Artículo de revista Journal of Computer-Aided Molecular Design, 29 (1), pp. 37-46, 2015, ISSN: 0920-654x. |
2013 |
Effect of Lithium on the Properties of a Liquid Crystal Formed by Sodium Dodecylsulphate and Decanol in Aqueous Solution Artículo de revista Journal of Chemical Physics, 139 (1), 2013, ISSN: 0021-9606. |