Lymphotactin: how a protein can adopt two folds

Metamorphic proteins like Lymphotactin are a notable exception of the empirical principle that structured natural proteins possess a unique three dimensional structure. In particular, the human chemokine lymphotactin protein (Ltn) exists in two distinct conformations (one monomeric and one dimeric) under physiological conditions. In this work we use a Ca Go-model to show how this very peculiar behavior can be reproduced. From the study of the thermodynamics and of the kinetics we characterize the interconversion mechanism. In particular, this takes place through the docking of the two chains living in a third monomeric, partially unfolded, state which shows a residual structure involving a set of local contacts common to the two native conformations. The main feature of two-fold proteins appears to be the sharing of a common set of local contacts between the two distinct folds as confirmed by the study of two designed two-fold proteins. Metamorphic proteins may be more common than expected.Comment: 14 pages, 4 figure

Properties of low-dimensional collective variables in the molecular dynamics of biopolymers

The description of the dynamics of a complex, high-dimensional system in terms of a low-dimensional set of collective variables Y can be fruitful if the low dimensional representation satisfies a Langevin equation with drift and diffusion coefficients which depend only on Y. We present a computational scheme to evaluate whether a given collective variable provides a faithful low-dimensional representation of the dynamics of a high-dimensional system. The scheme is based on the framework of finite-difference Langevin-equation, similar to that used for molecular-dynamics simulations. This allows one to calculate the drift and diffusion coefficients in any point of the full-dimensional system. The width of the distribution of drift and diffusion coefficients in an ensemble of microscopic points at the same value of Y indicates to which extent the dynamics of Y is described by a simple Langevin equation. Using a simple protein model we show that collective variables often used to describe biopolymers display a non-negligible width both in the drift and in the diffusion coefficients. We also show that the associated effective force is compatible with the equilibrium free--energy calculated from a microscopic sampling, but results in markedly different dynamical properties

Ratcheted molecular-dynamics simulations identify efficiently the transition state of protein folding

The atomistic characterization of the transition state is a fundamental step to improve the understanding of the folding mechanism and the function of proteins. From a computational point of view, the identification of the conformations that build out the transition state is particularly cumbersome, mainly because of the large computational cost of generating a statistically-sound set of folding trajectories. Here we show that a biasing algorithm, based on the physics of the ratchet-and-pawl, can be used to identify efficiently the transition state. The basic idea is that the algorithmic ratchet exerts a force on the protein when it is climbing the free-energy barrier, while it is inactive when it is descending. The transition state can be identified as the point of the trajectory where the ratchet changes regime. Besides discussing this strategy in general terms, we test it within a protein model whose transition state can be studied independently by plain molecular dynamics simulations. Finally, we show its power in explicit-solvent simulations, obtaining and characterizing a set of transition--state conformations for ACBP and CI2

The influence of Atlantic High on seasonal rainfall in Argentina

The objective of this work is to quantify the influence of the position and intensity of the Atlantic High (AH) on seasonal rainfall in Argentina. Monthly precipitation data in 68 stations from the National Meteorological Service of Argentina, the Secretariat of Water Resource and the Territorial Authority of the Limay, Neuquén, and Negro rivers basins (AIC) were used. Correlation was the methodology used to identify the link between seasonal rainfall and some indices especially defined to detect the position and intensity of the anticyclone. Precipitation composites of the years when the value of these indices was extremely high (greater than their second tercile) and extremely low (lower than their first tercile) were built for every season. They were analyzed and compared with humidity anomaly transport composites for the same sets of years in order to study circulation patterns associated with seasonal rainfall anomalies. Results indicate that when the AH is intensified, winter rainfall increases in central Argentina and spring rainfall increases in northern Cuyo region. When the AH is displaced towards the north of its mean position, autumn rainfall is favored in the northeast and central and south Patagonia, meanwhile winter and spring rainfall decreases in central Argentina. When the AH is displaced towards the east of its mean position, summer rainfall decreases in Central Andes. Finally, AH indices were used to detect the influence on rainfall in advance. Correlations between seasonal rainfall and the defined indices that characterize the anticyclone in the previous month suggest that there is some rainfall predictability, especially during spring in almost every region in Argentina.Fil: Garbarini, Eugenia María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: González, Marcela Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Rolla, Alfredo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentin

Metadynamic sampling of the free energy landscapes of proteins coupled with a Monte Carlo algorithm

Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus to gain an ever-increasing understanding on the general principles underlying the mechanism of protein folding. We show that it is possible to couple metadynamics and Monte Carlo algorithms to obtain the free energy of model proteins in a way which is computationally very economical.Comment: Submitted to Gen

Integrative structural and dynamical biology with PLUMED-ISDB

Accurate structural models of biological systems can be obtained by properly combining experimental data with a priori physico-chemical knowledge. Here we present PLUMED-ISDB, an open-source, freely-available module of the popular PLUMED library, which enables the simultaneous determination of structure and dynamics of conformationally heterogeneous systems by integrating experimental data with a priori information. This integration is achieved using metainference, a general Bayesian framework that accounts for both noise in the data and their ensemble-averaged nature. PLUMED-ISDB implements different types of experimental data, such as several NMR observables, FRET, SAXS and cryo-electron microscopy data, and enables modelling structure and dynamics of individual proteins, protein complexes, membrane proteins, RNA and DNA, using a variety of enhanced sampling methods and resolutions of the system

The new urban paradigm

This paper argues in favor of a new urban model that harnesses the power that cities have to curb global warming. Such a model tackles fundamental management challenges in the energy, building and transport sectors to promote the growth of diverse and compact cities. Such a model is essential for meeting complex challenges in cities, such as promoting a cohesive social life and a competitive economic base while simultaneously preserving agricultural and natural systems crucial to soil, energy, and material resources. With most of the population living in urban areas, the G20 should recognize the key role that cities play in addressing global challenges such as climate change. Improved measures taken by cities should be an indispensable solution. The G20 Development Working Group, Climate Sustainability Working Group, and Energy Transitions Working Group should incorporate an urban approach to discussions related to climate change.Fil: Lanfranchi, Gabriel. Centro de Implementación de Políticas Públicas para la Equidad y el Crecimiento; ArgentinaFil: Herrero, Ana Carolina. Centro de Implementación de Políticas Públicas para la Equidad y el Crecimiento; ArgentinaFil: Rueda Palenzuela, Salvador. Agencia Ecología Urbana Barcelona; EspañaFil: Camilloni, Ines Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; ArgentinaFil: Bauer, Steffen. German Development Institute; Alemani

Relationship between rainfall and streamflow in the La Plata Basin: annual cycles, interdecadal and multidecadal variability

The aim of this study is to understand the interaction between rainfall and streamflow variability in the La Plata basin (LPB) along a wide range of timescales. The LPB is divided in six sub-basins associated to the main rivers (Paraguay, Parana, Uruguay and Iguazu). The amplification of the streamflow response is addressed in order to evaluate to what extent river discharges variability can be explained by precipitation fluctuations. Mean annual cycles corresponding to 1931-2010 period and to each of the decades comprising it are analyzed. Streamflow interdecadal changes are observed in most of the gauging stations. In addition, an 11-year moving-average filter is applied to the normalized annual time series. Results exhibit a considerable higher percentage of explained variance in the streamflow filtered series, highlighting the predominance of medium and low frequencies variability present in these compared to those of precipitation. Consistently, river discharges show higher spectral density in the interdecadal/multidecadal frequencies compared to precipitation analysis. A simple statistical approach to advance in the understanding of the complex rainfall-streamflow physical relationship is addressed with promising results: streamflow spectrums are derived directly from the precipitation spectrum, transformed by a ´basin´ operator, characteristic of the basin itself. It is assumed that watersheds act on precipitation as spatio-temporal integrators operating as low-pass filters, like a moving average. Streamflow power spectrums are simulated assuming that the underlying process is an autoregressive moving average (ARMA). Considering as the only input the sub-basin areal-averaged precipitation timeseries, results show that simulated streamflow spectrums fits effectively the observations at the sub-basin scale.Fil: Gulizia, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Instituto Franco-Argentino sobre Estudios del Clima y sus Impactos; ArgentinaFil: Camilloni, Ines Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones del Mar y la Atmósfera. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones del Mar y la Atmósfera; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias de la Atmósfera y los Océanos; Argentina. Instituto Franco-Argentino sobre Estudios del Clima y sus Impactos; Argentin