Comportamiento de la amoxicilina en agua mediante métodos de solvatación implícita y explícita

El comportamiento molecular de la amoxicilina en agua fue explorado con solvatación implícita y explícita mediante dos estrategias que combinan diferentes técnicas de simulación molecular para evaluar el alcance de estos procedimientos. Con estas dos estrategias de cálculo computacional, la conformación molecular de la amoxicilina fue determinada en fase acuosa. En la primera estrategia se utilizó el generador de conformaciones Ballon-v1.8.2 y la estabilidad de las conformaciones en agua fue evaluada utilizando la energía libre de solvatación determinada con el método de solvatación implícita SMD. En la segunda estrategia, con la dinámica molecular tipo NVT fue evaluado el arreglo espacial de esta molécula en agua y, además, la interacción molecular entre la amoxicilina y el agua fue evaluada en esta simulación. Los resultados obtenidos muestran que la conformación de la amoxicilina más estable en fase acuosa es la plegada. Además, los valores de energías de solvatación de -121,42 y -14,58 kJ/mol obtenidos con solvatación implícita y dinámica molecular sugieren que esta molécula tiene una alta afinidad por el agua. Las funciones distribución radial y espacial sugieren que se forman 3 capas de solvatación alrededor de la amoxicilina y que esta molécula tiene una región altamente hidrofílica. Finalmente, la estrategia usando dinámica molecular permite obtener mejores conformaciones en equilibrio que la estrategia de simulación usando el generador de conformaciones Ballon-v1.8.2.

The molecular behavior of amoxicillin in water was explored with implicit and explicit solvation using two strategies that combine different molecular simulation techniques to assess the scope of these procedures. With these two computational calculation strategies, the molecular conformation of amoxicillin was determined in aqueous phase. In the first strategy, the conformation generator Ballon-v1.8.2 was used and the stability of the conformations in water was evaluated using the solvation free energy determined with the SMD implicit solvation method. In the second strategy, with NVT-type molecular dynamics, the spatial arrangement of this molecule in water was evaluated and, in addition, the molecular interaction between amoxicillin and water was evaluated in this simulation. The results obtained show that the most stable conformation of amoxicillin in the aqueous phase is the folded one. In addition, the solvation energy values of -121.42 and -14.58 kJ/mol obtained with implicit solvation and molecular dynamics suggest that this molecule has a high affinity for water. The radial and spatial distribution functions suggest that 3 solvation shells form around amoxicillin and that this molecule has a highly hydrophilic region. Finally, the strategy using molecular dynamics allows to obtain better equilibrium conformations than the simulation strategy using the Ballon-v1.8.2 conformation generator.

O comportamento da amoxicilina em água foi analisado com solvatação implícita e explícita mediante duas estratégias que combinam diferentes técnicas de simulação molecular para avaliar o escopo destes procedimentos. Com estas duas estratégias de cálculo computacional, a conformação molecular da amoxicilina foi determinada em fase aquosa. Na primeira estratégia, utilizou-se o gerador de conformação do software Ballon-v1.8.2 e avaliou-se a estabilidade das conformações em água a partir da energia livre de solvatação determinada pelo método de solvatação implícita SMD. Na segunda estratégia, avaliou-se o arranjo espacial da amoxicilina e sua interação com a água através de simulações de dinâmica molecular NVT. Os resultados obtidos mostram que a conformação dobrada é a mais estável em fase aquosa. Ademais, os valores de energía de solvatação de -121,42 e -14,58 kJ/mol obtidos com solvatação implícita e dinâmica molecular sugerem que esta molécula possui alta afinidade pela água. As funções de distribuição radial e espacial sugerem que se formam 3 camadas de solvatação ao redor da amoxicilina e que esta molécula possui uma região altamente hidrofílica. Finalmente, a estratégia usando dinâmica molecular permite obter melhores conformações de equilíbrio do que a estratégia de simulação usando o gerador de conformação do software Ballon-v1.8.2.

A bioinformatic approach to establish P38? MAPK inhibitory mechanism of selected natural products in psoriasis-Supplementary data

In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38? mitogen-activated protein kinases (P38? MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38? MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38? MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (?9.00 and ?8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action.

A bioinformatic approach to establish P38? MAPK inhibitory mechanism of selected natural products in psoriasis

In the present study, molecular docking studies of some selected natural products were carried out to identify the potential inhibitors and subsequently to suggest their mechanism of action in relation to P38? mitogen-activated protein kinases (P38? MAPK) enzyme. Psoriasis is an inflammatory disorder characterized by skin hyper-proliferation, differentiation in keratin expression, and increased production of pro-inflammatory cytokines. Increased expression of phosphorylated P38? MAPK in the cytoplasm and nucleus is observed in psoriatic lesions. Twelve natural antipsoriatic agents were included in the study and their molecular docking studies were carried out using AutoDock 4.2 simulator using a Lamarckian genetic algorithm. The crystal structure of P38? MAPK was retrieved from the protein data bank and three-dimensional chemical structures of natural ligands were prepared using ChemSketch 2015. Results indicated that all the natural ligands were fitted into the active site. Hypericin and Catechin (?9.00 and ?8.05 kcal/mol, respectively) have shown good binding efficacy among other ligands. However, only Epicatechin interacted with residues in the enzyme required for enzyme inhibition. The study concludes that the Epicatechin effectively inhibited the enzyme and proved itself to be a type-I1/2 inhibitor of the enzyme among other natural ligands and responsible for the treatment of psoriasis preclinically through this mechanism of action.

Volumetric behaviour of tetra-n-butyl ammonium bromidein various solvents at different temperatures / Comportamiento volumétrico del bromuro de tetra-n-butilamonio en varios solventes a diferentes temperaturas

ABSTRACT Measurement of ultrasonic velocity, density and viscosity of solutions of Tetra Butyl Ammonium Bromide have been carried outin different solvents (water, methanol, ethanol, 1-propanol and 1-butanol) as functions of concentration (1 to 0.1 M) at different temperatures (298.15 K to 318.15K). Using these experimental data, various acoustical and apparent parameters such as acoustical impedance, intermolecular free length, adiabatic compressibility, molar compressibility, Van der Waals constant, relaxation strength, apparent molar isentropic compressibility, apparent molar volume have been evaluated. Further, some thermodynamic parameters such as Gibbs free energy of activation, enthalpy and entropy of activation have been evaluated. All these parameters have been evaluated to understand type of interactions present in studied solutions.

RESUMEN La medición de la velocidad ultrasónica, la densidad y la viscosidad de algunas soluciones de bromuro de tetra-n-butilamonio se llevó a cabo en diferentes solventes (agua, metanol, etanol, 1-propanol y 1-butanol) en función de la concentración (1 a 0,1 M) y a diferentes temperaturas (298,15 K a 318.15 K). Utilizando estos datos experimentales, se evaluaron varios parámetros acústicos y aparentes, como la impedancia acústica, la longitud libre intermolecular, la compresibilidad adiabática, la compresibilidad molar, la constante de Van der Waals, la fuerza de relajación, la compresibilidad isentrópica molar aparente, el volumen molar aparente, etc. Además, se evaluaron algunos parámetros termodinâmicos, como la energía de activación libre de Gibbs, la entalpia y la entropía de activación. Todos estos parámetros han sido evaluados para comprender el tipo de interacciones presentes en las soluciones estudiadas.

Application of omics approaches in Sclerotinia sclerotiorum / 生物工程学报

Sclerotinia sclerotiorum is a typical necrotrophic plant pathogenic fungus that distributes worldwide and causes severe diseases on a broad-range of plant species. Studies on S. sclerotiorum have been mainly focused on biology and pathology. The development of high-throughput technologies enabled multi-omics approaches for systems biology. This review summarizes current researches on S. sclerotiorum and proposes systemic strategies for understanding its biology and pathology, to provide novel insights and references for further investigation on molecular biology and pathogenesis of the pathogenic fungi and the pathosystems.

Molar Refraction and Polarizability of Antiemetic drug 4-amino-5-chloro-N-(2-(diethylamino)ethyl)-2 methoxybenzamide hydrochloride monohydrate in {Aqueous-Sodium or Lithium Chloride} Solutions at 30oC.

The 4-amino-5-chloro-N-(2-(diethylamino)ethyl)-2 methoxybenzamide hydrochloride monohydrate exhibits antiemetic and parasympathomimetic activity. Density () and refractive index (nD) measurements were carried out as a function of drug concentration (c=0.01-0.11 mol·L-1) in aqueous NaCl/LiCl (c=0.05, 0.10 and 0.15 mol·L-1) solutions at 30oC. Linear relation of concentration dependence of density and refractive index were studied. Molar refractivity (RM) of solution was calculated from density and refractive index data and polarizability () was calculated from molar refractivity data. Stronger polarizability effects have been observed with increase in drug concentration.

Densities and speeds of sound of CaCl2, MgCl2, BaCl2 in aqueous 2-methoxy ethanol at 303K.

Densities(r), Viscosities(η) and ultrasonic speeds(U) of the electrolytes Calcium chloride(CaCl2), Magnesium Chloride(MgCl2) and Barium Chloride(BaCl2) in 5,15,25% of aqueous 2-Methoxy ethanol at 303K were measured over the entire composition range. From the experimental data, the internal pressure (pi), molar free volume (Vf), solvation number (Sn) and Viscosity B coefficients were calculated. The properties of the electrolytes are correlated with concentration of 2-Methoxy ethanol using the above parameters, which in turn are employed to predict the properties of electrolytes with good accuracy and are used to investigate the ion-ion and ion-solvent interactions present in the system.

Partial molar vllume of some alkanolamines in water at 298.15 k / Volumen molar parcial de algunas alcanolaminas en agua a 298,15 k / Volume molar paccial de algumas alcanolaminas em água a 298,15 k

Densities of aqueous solutions of 3-amino-1-propanol, 2-amino-1-propanol, 3-amino-1,2-propanediol, and 1,3-diamino-2-propanol were measured at 298.15 K using the vibrating tube technique. The apparent molar volumes of the alkanolamines were determined as a function of composition from experimental data and the solute limiting partial molar volume was obtained through extrapolation. The results are discussed in terms of the effect of the number and the position of polar groups in the molecules.

Las densidades de soluciones acuosas de 3-amino-1-propanol, 2-amino-1-propanol, 3-amino-1,2-propanodiol y 1,3-diamino-2-propanol fueron medidas a 298,15 K usando la técnica del tubo vibrante. Los volúmenes molares aparentes se determinaron en función de la composición a partir de los datos experimentales y los volúmenes molares parciales de los solutos a dilución infinita fueron obtenidos por extrapolación. Los resultados son discutidos en términos del efecto del número y la posición de los grupos polares en las moléculas.

As densidades de soluções aquosas de 3-amino-1-propanol, 2-amino-1-propanol, 3-amino-1,2-propanediol and 1,3-diamino-2-propanol foram medidas a 298 K utilizando a técnica de tubo vibratório. Os volumes molares aparentes das alcanolaminas foram determinados como uma função de composição partindo de dados experimentais e parciais volumes molares de solutos na diluição infinita foram obtidos por extrapolação. Os resultados são discutidos em termos do efeito do número e da posição dos grupos polares nas moléculas.