Recent developments of GROMACS v.2016 ceased to support methodological approaches used in the development and validation of the GROMOS force field. We investigated the performance of a previously developed extension of the GROMOS force field for lipopolysaccharides to reproduce the structural dynamics of bacterial outer membrane (OM) using a single cutoff for nonbonded interactions and atom-based charge truncation. We further compared this setup for use with reaction field (RF) or particle mesh Ewald (PME) approximations in the presence of simple point charge (SPC) and extended simple point charge (SPC/E) water models. We find that the OM structural dynamics is well conserved in all simulated conditions, reproducing the available experimental data within the measurement uncertainty. The SPC/E model induces a small increase in OM fluidity, and when combined with the RF correction, shows a decrease in water orientation at the membrane surface. The present simulations support the compatibility of the GROMOS-derived lipopolysaccharide (LPS) parameters for use with single cutoff and atom-based charge schemes, either with RF or PME approximations, in GROMACS v.2016. Both SPC and SPC/E water models are suitable for use, but usage of SPC/E combined with the reaction field correction needs to be further investigated.

The accumulation of antibiotics in wastewater has led to the development and spreading of antibiotic resistance in the environment. Amoxicillin (Amox), a beta-lactamic antibiotic, is one of the most frequently consumed antibiotics in the world. We have applied two metal-organic frameworks (MOFs) containing zinc(II) as platforms to degrade Amox. We have predicted the adsorption of this antibiotic via molecular docking calculations which have been further corroborated by means of Fourier transform infrared and UV-Vis spectroscopies, thermogravimetric analysis, X-ray diffraction and scanning microscopy measurements. We have subsequently performed mass spectrometry analysis of Amox@zeolitic imidazolate framework-8 (ZIF-8) and Amox@Zn(1,4-benzenedicarboxylate) (ZnBDC) to demonstrate the degradation of Amox upon contact with the Zn-containing frameworks. We propose a possible pathway for the degradation of Amox involving the cleavage of the four-membered β-lactam ring. These Zn-containing frameworks provide a biocompatible platform for the degradation in solution of Amox, which should also be suitable to degrade other β-lactam antibiotics.

Surfactants are molecular structures with remarkable physicochemical properties and applications. Most of their characteristics are due to their ability to promote aggregation and interactions with different interfaces. The scarcity of theoretical studies dedicated to evaluating the forces involved in these interactions prompted us to propose other models capable of reproducing the experimental data in better ways. We carried out molecular dynamics (MD) simulations to obtain a model for cetyltrimethylammonium bromide (CTAB), selected from gromos54a7 force field parameters, that better describes most of its behaviors in aqueous solution (micellar structure, counterion dissociation, etc.) and its adsorption pattern on a gold surface. The parameters adopted for one of the models were able to mimic several characteristics suggested by experimental measurements of the CTAB micelles, as well their adsorption pattern on a gold surface. Indeed, this model was able to obtain quasi-spherical micelles, as well as a pattern of adjacent cylindrical micelles with alkyl chain interactions on a gold surface.

Glutathione S-transferases (GSTs) are enzymes capable of metabolizing cytotoxic compounds. The enzyme AgGSTE2, member of epsilon class GSTs (GSTE), is the most important GST conferring resistance to dichloro-diphenyl-trichloroethane (DDT) in Anopheles gambiae. We have investigated the conformational dynamics of three GSTE variants (GSTE2, GSTE2-I114T/F120L, GSTE5) from A. gambiae. Large-scale motions of helices H2 and H4 and conformational transition of the C-terminal governs the opening of the G-site and is expected to affect substrate binding and product release. This structural rearrangement places Glu116 (Glu120 in GSTE5) close of the thiol group of the tripeptide glutathione (GSH) cofactor, making this residue a candidate to act as a base in the activation of DDT. The structural rearrangement is noticeable for AgGSTE2-F120L, which has been shown to confer increased DDT-resistance. The other variants exhibit a more subtle rearrangement. These findings corroborate the hypothesis that the increase of the conformational dynamics of GST Epsilon class isoforms from A. gambiae promotes higher DDTase activity.

Lipopolissacarídeos são os principais constituintes da membrana externa de bactérias Gram-negativas. Esta classe de compostos desempenha um papel fundamental em processos químicos mediados por estas bactérias como o reconhecimento e ligação de metais, adesão a superfícies e reações de óxido-redução. Lipopolissacarídeos são também os mais comuns agentes causadores de doenças nosocomiais que levam a infecções crônicas e agudas em pacientes de queimaduras, deficiência imunológica e fibrose cística. Variação fenotípica na expressão de bandas A e B em membranas lipopolissacarídicas de P. aeruginosa resultam em mudanças de propriedades químicas da superfície bacteriana que afetam a adesão bacteriana a superfícies celulares e favorecem a sobrevivência do organismo. Simulações de dinâmica molecular clássica em solvente explícito foram realizadas para a membrana lipopolissacarídica lisa (A-B+ LPS) de Pseudomonas aeruginosa por um período de 12 ns. A banda B exibe uma grande flexibilidade e permanece solvatada durante o período de simulação. Interações de longo alcance entre a banda B e as moléculas de carboidratos na superfície da membrana não foram observadas corroborando resultados postulados anteriormente através de experimentos de microscopia de forca atômica. Comparações com simulações da membrana lipopolissacarídica rugosa (A-B- LPS) de P. aeruginosa indicam que a presença da banda B induz uma expansão da membrana e modifica drasticamente tanto o potencial eletrostático através da membrana como a distribuição de cargas na superfície da mesma. Estes resultados oferecem uma explicação para o fato de que apenas as cepas de P. aeruginosa que contem a banda B são capazes de se aderirem a superfícies celulares, e para a necessidade de perda da banda B para que então estes organismos possam iniciar uma infecção aguda em adição à infecção crônica do paciente.

Lipopolysaccharides (LPSs) form the major constituent of the outer membrane of Gram-negative bacteria, and are believed to play a key role in processes that govern microbial metal binding, surface adhesion, and microbe-mediated oxidation/reduction reactions. It is also a major causative agent of nosocomial illness, eliciting both chronic and acute infections in burn, immunocompromised, and cystic fibrosis. Phenotypic variation in the relative expression of A- and B-band in the LPS of Pseudomonas aeruginosa seems to alter its overall surface characteristics influencing adhesion and favoring survival. Classical molecular dynamics simulations of A-B+ LPS membrane model of P. aeruginosa were carried out in explicit solvent for 12+ ns. The B-band presents a remarkable flexibility remaining fully solvated and does not interact with the sugar units from the LPS core surface residues, in agreement with atomic force microscopy experiments. Comparison with previous simulations of the rough LPS membrane suggests that the presence of the B-band promotes membrane expansion. In addition, this O-antigen chain dramatically alters the electrostatic potential and surface charge of the LPS membrane. This is illustrated by the resulting electrostatic surface potential. These results are compared to previous simulations of the rough LPS and a model hypothesis is proposed to explain the increased ability of B-band expressing microorganisms to adhere to cell surfaces and the necessity of these organisms to loose the O side chain for the development of acute infections.

The ability of biomolecules to catalyze chemical reactions is due chiefly to their sensitivity to variations of the pH in the surrounding environment. The reason for this is that they are made up of chemical groups whose ionization states are modulated by pH changes that are of the order of 0.4 units. The determination of the protonation states of such chemical groups as a function of conformation of the biomolecule and the pH of the environment can be useful in the elucidation of important biological processes from enzymatic catalysis to protein folding and molecular recognition. In the past 15 years, the theory of Poisson-Boltzmann has been successfully used to estimate the pKa of ionizable sites in proteins yielding results, which may differ by 0.1 unit from the experimental values. In this study, we review the theory of Poisson-Boltzmann under the perspective of its application to the calculation of pKa in proteins.