RESUMO
The mechanism that arginine-rich cell penetrating peptides (ARCPPs) use to translocate lipid membranes is not entirely understood. In the present work, we develop a molecular theory that allows to investigate the adsorption and insertion of ARCPPs on membranes bearing hydrophilic pores. This method accounts for size, shape, conformation, protonation state and charge distribution of the peptides; it also describes the state of protonation of acidic membrane lipids. We present a systematic investigation of the effect of pore size, peptide concentration and sequence length on the extent of peptide adsorption and insertion into the pores. We show that adsorption on the intact (non-porated) lipid membrane plays a key role on peptide translocation. For peptides shorter than nona-arginine, adsorption on the intact membrane increases significantly with chain length, but it saturates for longer peptides. However, this adsorption behavior only occurs at relatively low peptide concentrations; increasing peptide concentration favors adsorption of the shorter molecules. Adsorption of longer peptides increases the intact membrane negative charge as a result of further deprotonation of acidic lipids. Peptide insertion into the pores depends non-monotonically on pore radius, which reflects the short range nature of the effective membrane-peptide interactions. The size of the pore that promotes maximum adsorption depends on the peptide chain length. Peptide translocation is a thermally activated process, so we complement our thermodynamic approach with a simple kinetic model that allows to rationalize the ARCPPs translocation rate in terms of the free energy gain of adsorption, and the energy cost of creating a transmembrane pore with peptides in it. Our results indicate that strategies to improve translocation efficiency should focus on enhancing peptide adsorption.
Assuntos
Peptídeos Penetradores de Células/química , Bicamadas Lipídicas/química , Peptídeos/química , Termodinâmica , Adsorção , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Estrutura Molecular , Tamanho da Partícula , Eletricidade Estática , Propriedades de SuperfícieRESUMO
Motivation: Chemical shifts (CS) are an important source of structural information of macromolecules such as RNA. In addition to the scarce availability of CS for RNA, the observed values are prone to errors due to a wrong re-calibration or miss assignments. Different groups have dedicated their efforts to correct CS systematic errors on RNA. Despite this, there are not automated and freely available algorithms for evaluating the referencing of RNA 13 C CS before their deposition to the BMRB or re-reference already deposited CS with systematic errors. Results: Based on an existent method we have implemented an open source python module to correct 13 C CS (from here on 13Cexp) systematic errors of RNAs and then return the results in 3 formats including the nmrstar one. Availability and implementation: This software is available on GitHub at https://github.com/BIOS-IMASL/13Check_RNA under a MIT license. Supplementary information: Supplementary data are available at Bioinformatics online.
Assuntos
Isótopos de Carbono/análise , RNA/química , Software , Biologia Computacional , Análise de Sequência de RNARESUMO
Dissipative self-assembly is the formation of ordered structures far from equilibrium, which continuously uptake energy and dissipate it into the environment. Due to its dynamical nature, dissipative self-assembly can lead to new phenomena and possibilities of self-organization that are unavailable to equilibrium systems. Understanding the dynamics of dissipative self-assembly is required in order to direct the assembly to structures of interest. In the present work, Brownian dynamics simulations and analytical theory were used to study the dynamics of self-assembly of a mixture of particles coated with weak acids and bases under continuous oscillations of the pH. The pH of the system modulates the charge of the particles and, therefore, the interparticle forces oscillate in time. This system produces a variety of self-assembled structures, including colloidal molecules, fibers and different types of crystalline lattices. The most important conclusions of our study are: (i) in the limit of fast oscillations, the whole dynamics (and not only those at the non-equilibrium steady state) of a system of particles interacting through time-oscillating interparticle forces can be described by an effective potential that is the time average of the time-dependent potential over one oscillation period; (ii) the oscillation period is critical to determine the order of the system. In some cases the order is favored by very fast oscillations while in others small oscillation frequencies increase the order. In the latter case, it is shown that slow oscillations remove kinetic traps and, thus, allow the system to evolve towards the most stable non-equilibrium steady state.
Assuntos
Coloides/química , Dimerização , Concentração de Íons de Hidrogênio , Cinética , Simulação de Dinâmica Molecular , Periodicidade , TermodinâmicaRESUMO
We use a molecular theory to study the thermodynamics of a weak-polyacid hydrogel film that is chemically grafted to a solid surface. We investigate the response of the material to changes in the pH and salt concentration of the buffer solution. Our results show that the pH-triggered swelling of the hydrogel film has a non-monotonic dependence on the acidity of the bath solution. At most salt concentrations, the thickness of the hydrogel film presents a maximum when the pH of the solution is increased from acidic values. The quantitative details of such swelling behavior, which is not observed when the film is physically deposited on the surface, depend on the molecular architecture of the polymer network. This swelling-deswelling transition is the consequence of the complex interplay between the chemical free energy (acid-base equilibrium), the electrostatic repulsions between charged monomers, which are both modulated by the absorption of ions, and the ability of the polymer network to regulate charge and control its volume (molecular organization). In the absence of such competition, for example, for high salt concentrations, the film swells monotonically with increasing pH. A deswelling-swelling transition is similarly predicted as a function of the salt concentration at intermediate pH values. This reentrant behavior, which is due to the coupling between charge regulation and the two opposing effects triggered by salt concentration (screening electrostatic interactions and charging/discharging the acid groups), is similar to that found in end-grafted weak polyelectrolyte layers. Understanding how to control the response of the material to different stimuli, in terms of its molecular structure and local chemical composition, can help the targeted design of applications with extended functionality. We describe the response of the material to an applied pressure and an electric potential. We present profiles that outline the local chemical composition of the hydrogel, which can be useful information when designing applications that pursue or require the absorption of biomolecules or pH-sensitive molecules within different regions of the film.
Assuntos
Hidrogéis/química , Sais/química , Concentração de Íons de Hidrogênio , Modelos Moleculares , Eletricidade Estática , TermodinâmicaRESUMO
The structure of water clusters (H(2)O)(n) (n = 40-200) and bulk water were examined by molecular dynamics simulations using the TIP4P-ice water model. The analysis of the low-temperature structures in terms of the local structure index (LSI) showed a bimodal distribution. This finding supports the two-state picture derived from the analysis of the inherent dynamics of bulk SPC/E water. The water molecules at the outer interface of the coldest clusters are more structured than those in the inner core. The geometrical constraint of the interface forces the surface molecules to lose one neighbor and adopt a local angular distribution of hydrogen bonds resembling that found in the basal plane of ice Ih.