QCAR models to predict wild mushrooms radical scavenging activity, reducing power and lipid peroxidation inhibition

Wild mushrooms have become attractive as a source of physiologically beneficial compounds including antioxidants such as phenolic compounds and tocopherols. The concentrations of antioxidant compounds (phenolics and α-tocopherol) and EC50 values of antioxidant activity (concentration required to achieve 50% of radical scavenging activity and lipid peroxidation inhibition, or 0.5 of absorbance in reducing power) were analyzed by partial least square (PLS) regression analysis. Three QCAR (Quantitative Composition-Activity Relationship) models were constructed and their robustness and predictability were verified by internal and external cross-validation methods. Antioxidant activity correlated well with phenolics and -tocopherol contents, the major antioxidants in wild mushrooms. The models proved to be useful tools in the prediction of mushrooms radical scavenging activity, reducing power and lipid peroxidation inhibition

Using molecular docking to investigate the anti-breast cancer activity of low molecular weight compounds present on wild mushrooms.

Mushrooms represent an unlimited source of compounds with antitumor and immunostimulating properties and mushroom intake as been shown to reduce the risk of breast cancer. A large number of LMW (low molecular weight) compounds present in mushrooms have been identified including: phenolic acids, flavonoids, tocopherols, carotenoids, sugars and fatty acids. In order to evaluate which wild mushroom LMW compounds may be involved in anti-breast cancer activity we selected a representative dataset of 43 LMW compounds and performed molecular docking against 3 known protein targets involved in breast cancer (Aromatase, Estrone Sulfatase and 17β-HSD-1) using AutoDock4 as docking software. The estimated inhibition constants for all LMW compounds were determined and the potential structure-activity relationships for the compounds with the best estimated inhibition constants are discussed for each compound family. 4-O-caffeoylquinic, naringin and lycopene stand out as the top ranked potential inhibitors for Aromatase, Estrone Sulfatase and 17β-HSD1, respectively, and the 3-D docked conformation for these compounds are discussed in detail. This information provides several interesting starting points for further development of Aromatase, Estrone Sulfatase and 17β-HSD1 inhibitors

Virtual ligand screening studies between mushroom compounds and proteins involved in breast cancer

Mushrooms are a vast and yet largely untapped source of powerful new pharmaceutical products. In particular, and most importantly for modern medicine, they represent an unlimited source of compounds with antitumor and immunostimulating properties [1]. Particularly, the intake of some wild mushrooms has shown to reduce the risk of breast cancer in Chinese women [2]. A large number of LMW (low molecular weight) compounds have been "identified in wild mushrooms including phenolic acids, flavonoids, tocopherols, carotenoids, sugars and fatty acids [3]. In this study we used AutoDock 4 [4] to perform virtual ligand screening in order to evaluate which LMW compounds may be involved in the inhibition of the activity of proteins related to human breast cancer: aromatase (EC: 1.14.14.1), estrone sulfatase (EC: 3.1.6.2) and 17- hydroxysteroid dehydrogenase type 1 activity (17~-HSD-1; EC:. 1.1.1.62) [5]. A representative dataset of 43 LMW compounds was selected and molecular docking was performed against the three protein targets. 4-0-caffeoylquinic, naringin and lycopene stand out as the top ranked potential inhibitors for aromatase, estrone sulfatase and 1 7~HSD1, respectively. The information provided shows several interesting starting points for further development of inhibitors of the studied proteins, as also for the development of nutraceuticals or functional foods

Valorização de cogumelos silvestres como alimentos funcionais: estudos de química computacional

As interacções intermoleculares desempenham um papel essencial nos diversos processos biológicos, sendo fundamental a compreensão destas interacções nos Sectores das Indústrias Farmacêuticas e de Alimentos Funcionais. Os cogumelos representam uma fonte ilimitada de compostos com propriedades antitumorais e imunoestimulantes, e o seu consumo foi já relacionado com a redução do risco de cancro da mama. No presente trabalho, foram desenvolvidos dois estudos in silico com o intuito de compreender algumas das interacções moleculares presentes em cogumelos e responsáveis pela sua bioactividade. A técnica dos Mínimos Quadrados Parciais foi utilizada para avaliar a relação entre o potencial antioxidante (efeitos bloqueadores de radicais livres e poder redutor) e a composição química de vinte e três amostras de dezassete espécies de cogumelos silvestres Portugueses. Estudaram-se vários parâmetros analíticos tais como cinzas, hidratos de carbono, proteínas, gorduras, ácidos gordos monoinsaturados, ácidos gordos polinsaturados, ácidos gordos saturados, fenóis, flavonóides, ácido ascórbico e β-caroteno, e os seus resultados foram analisados pela técnica anteriormente mencionada de forma a estabelecer correlações entre todos os parâmetros. A actividade antioxidante mostrou estar correlacionada com o teor em fenóis e flavonóides. Foi construído um modelo QCAR (Relações Quantitativas Composição – Actividade), cuja robustez e previsibilidade foram verificadas por métodos de validação cruzada internos e externos. Finalmente, este modelo provou ser uma ferramenta útil na previsão do poder redutor de cogumelos

Docking studies to evaluate mushrooms low molecular weight compounds as inhibitors of the anti-apoptotic protein BCL-2

Several reports indicate that mushrooms have the ability to promote apoptosis in tumour cell lines, but the mechanism of action is not quite well understood. Inhibition of the interaction between Bcl-2 (anti-apoptotic protein) and pro-apoptotic proteins could be an important step that leads to apoptosis. Therefore, the discovery of compounds with the capacity to inhibit Bcl-2 is an ongoing research topic on cancer therapy. Herein, Autodock4 virtual screening was applied to a dataset of 40 low molecular weight compounds present in mushrooms, using 3D Bcl-2 protein structure (PDB:2XA0) as target. Results suggested that steroids mainly ergosta-4,6,8(14),22-tetraen-3-one, lucidenic lactone, cerevisterol, ganoderic acid w and ganoderic acid x, with a binding energy lower than -10 kcal/mol, had the ability to interact with Bcl-2

A Monte-Carlo generator for statistical hadronization in high energy e+e- collisions

We present a Monte-Carlo implementation of the Statistical Hadronization Model in e+e- collisions. The physical scheme is based on the statistical hadronization of massive clusters produced by the event generator Herwig within the microcanonical ensemble. We present a preliminary comparison of several observables with measurements in e+e- collisions at the Z peak. Although a fine tuning of the model parameters is not carried out, a general good agreement between its predictions and data is found.Comment: 19 pages, 28 figures, 6 tables. v2: added sections on comparison between the Statistical Hadronization Model and the Cluster Model and on the interplay between Herwig cluster splitting algorithm and Statistical Hadronization Model predictions. Fixed typos and references added. Version accepted for publication in EPJ

MOLA: a tool for automation of parallel virtual docking using AutoDock Vina in a heterogeneous set of computer clusters

The use of molecular docking lo search large databases of compounds for possible ligands of a protein receptor is usually termed virtual screening and has been successfully applied in several therapeutic programs at the lead discovery stage. However, large scale virtual screening is lime demanding and usually requires dedicated High Performance Computing (H PC) systems

Creation of antimicrobial biopolymers by the use of recombinant DNA technology

[Excerpt] The spread of antimicrobials resistant microorganisms has triggered the search for new ways to treat infections. One of these ways is the creation of antimicrobial devices and surfaces that kill or prevent the spread of microorganisms. In the present work we explored the properties of different antimicrobial peptides (AMPs) for the creation of biopolymers with broad antimicrobial activity. Antimicrobial recombinant protein-based polymers (rPBPs) were designed by cloning the DNA sequence coding for the different AMPs in frame with the N-terminus of the elastin-like recombinamer consisting of 200 repetitions of the pentamer VPAVG, here named A200. [...]This work was supported by the strategic programme UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) funded by national funds through the FCT I.P. and by the ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI). By the Spanish Minister of Economy and Competitiveness (MAT2012-38043-C02-01) and Junta de Castilla y León-JCyL (VA152A12-2 and VA155A12-2), Spain. AC and RM, acknowledge FCT for SFRH/BD/75882/2011 and SFRH/BPD/86470/2012 grants, respectively

The Safe-Port project: an approach to port surveillance and protection

SAFE-PORT is a recently started project addressing the complex issue of determining the best configurations of resources for harbour and port surveillance and protection. More specifically, the main goal is to find, for any given scenario, an adequate set of configuration solutions — i.e., number and type of sensors and equipments, their locations and operating modes, the corresponding personnel and other support resources — that maximize protection over a specific area. The project includes research and development of sensors models, novel algorithms for optimization and decision support, and a computer-based decision support system (DSS) to assist decision makers in that task. It includes also the development of a simulation environment for modelling relevant aspects of the scenario (including sensors used for surveillance, platforms, threats and the environment), capable to incorporate data from field-trials, used to test and validate solutions proposed by the DSS. Test cases will consider the use of intelligent agents to model the behaviour of threats and of NATO forces in a realistic way, following experts’ definitions and parameters