Hofmeister series for metal-cation–RNA interactions: the interplay of binding affinity and exchange kinetics

A large variety of physicochemical properties involving RNA depends on the type of metal cation present in solution. In order to gain microscopic insight into the origin of these ion specific effects, we apply molecular dynamics simulations to describe the interactions of metal cations and RNA. For the three most common ion binding sites on RNA, we calculate the binding affinities and exchange rates of eight different mono- and divalent metal cations. Our results reveal that binding sites involving phosphate groups preferentially bind metal cations with high charge density (such as Mg2+) in inner-sphere conformations while binding sites involving N7 or O6 atoms preferentially bind cations with low charge density (such as K+). The binding affinity therefore follows a direct Hofmeister series at the backbone but is reversed at the nucleobases leading to a high selectivity of ion binding sites on RNA. In addition, the exchange rates for cation binding cover almost 5 orders of magnitude, leading to a vastly different time scale for the lifetimes of contact pairs. Taken together, the site-specific binding affinities and the specific lifetime of contact pairs provide the microscopic explanation of ion specific effects observed in a wide variety of macroscopic RNA properties. Finally, combining the results from atomistic simulations with extended Poisson-Boltzmann theory allows us to predict the distribution of metal cations around double-stranded RNA at finite concentrations and to reproduce the results of ion counting experiments with good accuracy

Optimized magnesium force field parameters for biomolecular simulations with accurate solvation, ion-binding, and water-exchange properties

Magnesium ions play an essential role in many vital processes. To correctly describe their interactions in molecular dynamics simulations, an accurate parametrization is crucial. Despite the importance and considerable scientific effort, current force fields based on the commonly used 12-6 Lennard-Jones interaction potential fail to reproduce a variety of experimental solution properties. In particular, no parametrization exists so far that simultaneously reproduces the solvation free energy and the distance to the water oxygens in the first hydration shell. Moreover, current Mg2+ force fields significantly underestimate the rate of water exchange leading to unrealistically slow exchange kinetics. In order to make progress in the development of improved models, we systematically optimize the Mg2+ parameters in combination with the TIP3P water model in a much larger parameter space than previously done. The results show that a long-ranged interaction potential and modified Lorentz-Berthelot combination rules allow us to accurately reproduce multiple experimental properties including the solvation free energy, the distances to the oxygens of the first hydration shell, the hydration number, the activity coefficient derivative in MgCl2 solutions, the self-diffusion coefficient, and the binding affinity to the phosphate oxygen of RNA. Matching this broad range of thermodynamic properties, we present two sets of optimal parameters: MicroMg yields water exchange on the microsecond timescale in agreement with experiments. NanoMg yields water exchange on the nanosecond timescale facilitating the direct observation of ion-binding events. As shown for the example of the add A-riboswitch, the optimized parameters correctly reproduce the structure of specifically bound ions and permit the de novo prediction of Mg2+-binding sites in biomolecular simulations

RBCC-E Triad

Comunicación presentada en: Brewer Ozone Spectrophotometer/Metrology Open Workshop celebrado del 17 al 20 de mayo de 2016 en Ponta Delgada, Azores, Portugal

Brewer-OMI validation

Presentación realizada en: Brewer Ozone Spectrophotometer/Metrology Open Workshop, celebrado en Ponta Delgada (Sao Miguel, Azores) del 17 al 20 de mayo de 2016

The Regional Brewer Calibration Center - Europe: an overview of the X Brewer Intercomparison Campaign

Comunicación presentada en: TECO-2016 (Technical Conference on Meteorological and Environmental Instruments and Methods of Observation) celebrada en Madrid, del 27 al 30 de septiembre de 2016.The X Regional Brewer Calibration Center - Europe (RBCC-E) intercomparison campaign was held at El Arenosillo atmospheric sounding station of the Instituto Nacional de Tecnica Aeroespacial (INTA) during the period of May 25th – June 5th, 2015. This X Brewer intercomparison campaign was a joint effort of EUBREWNET and the Area of Instrumentation and Atmospheric Research of INTA, with the support of COST Action 1207. Twenty one Brewer instruments from eleven countries participated at the El Arenosillo campaign. In addition, the solar UV irradiance calibration was performed by the traveling reference standard QASUME of the World Calibration Center for UV (WCC-UV). This work shows a general overview of the ozone comparison focused on the correction of the stray light effect for the single-monochromator Brewer spectrophotometer derived by the comparison with a reference double-monochromator Brewer. At the beginning of the campaign, 16 out of the 21 participating Brewer instruments (76%) agreed to better than ± 1%, and 10 instruments (50%) agreed to better than ± 0.5%. After applying the final calibration that included the stray light correction, all working instruments agreed at the ± 0.5% level

Preliminar results on the operative cosine correction in EUBREWNET

Póster elaborado para el Quadrennial Ozone Symposium celebrado en Edinburgh los días 4–9 de septiembre de 2016

Aerosol Optical Depth

Presentación realizada en: Quadrennial Ozone Symposium, celebrado en Edimburgo del 4 al 9 de septiembre de 2016

Stability of the RBCC-E Triad during the period 2005 - 2015

Póster elaborado para el Quadrennial Ozone Symposium celebrado en Edinburgh los días 4–9 de septiembre de 2016

Aerosol Optical Depth: configuration

Presentación realizada en: Quadrennial Ozone Symposium, celebrado en Edimburgo del 4 al 9 de septiembre de 2016