Jorge Peña-García

Developing science gateways for drug discovery in a grid environment

BackgroundMethods for in silico screening of large databases of molecules increasingly complement and replace experimental techniques to discover novel compounds to combat diseases. As these techniques become more complex and computationally costly we are faced with an increasing problem to provide the research community of life sciences with a convenient tool for high-throughput virtual screening on distributed computing resources.ResultsTo this end, we recently integrated the biophysics-based drug-screening program FlexScreen into a service, applicable for large-scale parallel screening and reusable in the context of scientific workflows.ConclusionsOur implementation is based on Pipeline Pilot and Simple Object Access Protocol and provides an easy-to-use graphical user interface to construct complex workflows, which can be executed on distributed computing resources, thus accelerating the throughput by several orders of magnitude.

Enhancing the Parallelization of Non-bonded Interactions Kernel for Virtual Screening on GPUs

Virtual Screening (VS) methods can considerably aid clinical research, predicting how ligands interact with drug targets. Most VS methods suppose a unique binding site for the target, usually derived from the interpretation of the protein crystal structure. But it has been demonstrated that in many cases, diverse ligands interact with unrelated parts of the target and many VS methods do not take into account this relevant fact.However, this fact increases the computationally complexity exponentially. In this work we enhance the parallelization of non-bonded interactions kernel for VS methods on Nvidia GPU architectures. We show several parallelization strategies that lead to a speed up factor of 15x compared to previous GPU implementations.

Chitosan as stabilizing agent for negatively charged nanoparticles

Chitosan is a biocompatible polysaccharide with positive Z potential which can stabilize negative charged nanoparticles. Silk fibroin nanoparticles and citrate gold nanoparticles, both with negative Z potential, but they form aggregates at physiological ionic strength. In this work, we study the behavior of chitosan in solution when the ionic strength of the medium is increased and how the concentration of chitosan and the proportion of the two components (chitosan and AuNP or SFN) significantly affect the stability and size of the nanocomposites formed. In addition to experimental measurements, molecular modeling were used to gain insight into how chitosan interacts with silk fibroin monomers, and to identify the main energetic interactions involved in the process. The optimum values for obtaining the smallest and most homogeneous stable nanocomposites were obtained and two different ways of organization through which chitosan may exert its stabilizing effect were suggested.

Sedative-hypnotic-like effect and molecular docking of di-naphthodiospyrol from Diospyros lotus in an animal model

BACKGROUND Diospyros lotus Linn commonly known as date-plum, or Caucasian persimmon has multiple uses in folk medicine. Various parts of this plant is used for alleviating lumbago, dysponea, hemorrhage, insomnia, and hiccup. The plant extracts possess a variety of biological activities, such as anti-inflammatory, sedative, febrifuge, anti-microbial, vermifuge, and anti-hypertensive. AIM/HYPOTHESIS The aim of the present work is to investigate the sedative-hypnotic effect of a rare dimeric napthoquione 1 obtained from the chloroform soluble fraction of D. lotus extracts. METHODS Compound 1, di-naphthodiospyrol at 5, 10, and 15mg/kg intraperitoneal doses was assessed for its in vivo sedative effect in an open-field using a phenobarbitone-induced sleeping time model. The geometry of di-naphthodiospyrol was also optimized with the aid of density functional theory. In addition, molecular docking of compound 1 was performed with the receptor GABAA. RESULTS The animal protocol-based assay showed significant sedative-hypnotic-like effects of compound 1 at various test doses (5, 10, and 15mg/kg i.p.). Docking studies indicated that this compound interacts strongly with important residues in receptor GABAA. CONCLUSIONS Results from this investigation reveal that compound 1 possesses sedative-hypnotic- like properties which can be of interest in therapeutic research.

Improving Activity Prediction of Adenosine A2B Receptor Antagonists by Nonlinear Models

This study deals on estimation of ligand activity with its descriptors. So, to achieve this goal, two different approaches were implemented. In the first one, the intervals between samples were determined. But in the second method, the intervals were clustered with k-means method. Afterwards, best descriptors of each ligands were extracted with genetic algorithm. Then, observations were classified with One-Against-All method. Finally, the activity of each ligands were estimated by forty percent of samples. In the first method, AUC values were between fifty four to ninety seven percent. For second approaches, there were about ninety seven percent.

DIA-DB: A Web-Accessible Database for the Prediction of Diabetes Drugs

Diabetes mellitus is the 8th leading cause of death worldwide, with 1.5 million deaths in 2012, and medical costs that reached 245

In vitro modulatory effects of functionalized pyrimidines and piperidine derivatives on Aryl hydrocarbon receptor (AhR) and glucocorticoid receptor (GR) activities

billion in the US. Moreover, it is estimated that roughly 387 million people worldwide suffer from diabetes mellitus, with numbers growing rapidly. These facts demonstrate the importance of creating a completely new and innovative method for the fast development of novel anti-diabetic compounds. In silico prediction methods represent an efficient approach for the prediction of diabetes drugs, aiming to explaining preclinical drug development and therefore enabling the reduction of associated time, costs and experiments. We present here DIA-DB, a web server for the prediction of diabetes drugs that uses two different approaches; a) comparison by similarity with a curated database of anti-diabetic drugs and experimental compounds, and b) inverse virtual screening of the input molecules chosen by the users against a set of protein targets identified as key elements in diabetes. The server is open to all users and is accessible at http://bio-hpc.eu/dia-db , where registration is not necessary, and a detailed report with the prediction results are sent to the user by email once calculations are finished. This is the first public domain database for diabetes drugs.

HYDROWEB, an Online Tool for the Calculation of Hydrodynamic Properties of Macromolecules

The development of biologically active molecules based on molecular recognition is an attractive and challenging task in medicinal chemistry and the molecules that can activate/deactivate certain receptors are of great medical interest. In this contribution, selected pyrimidine/piperidine derivatives were synthesized and tested for the ability to activate/deactivate Aryl hydrocarbon receptor (AhR) and Glucocorticoid receptor (GR). Tested compounds are shown to activate the receptors but to much lesser extent than positive controls, dioxin and dexamethasone for Ahr and GR, respectively. However, some of them antagonized the positive controls action. Although further in vivo studies are needed to fully characterize the bioactivities of these compounds, the reported in vitro evidences demonstrate that they might be used as the modulators of AhR and GR activities.

Exploiting the cyclodextrins ability for antioxidants encapsulation: A computational approach to carnosol and carnosic acid embedding

Calculation and prediction of hydrodynamic properties of biological and synthetic macromolecules through computational approaches is a technique that has experimented a great advance in the last decades. However, most of the hydrodynamics software was designed decades ago and it is rather complex to use for less computer experienced users. With this objective in mind we have developed HYDROWEB, a tool that easily allows to work with hydrodynamic models of macromolecules and the calculation of their properties (using the softwares HYDROPRO, HYDRO++ and SIMUFLEX) and convenient visualization of its results. The tool can be accessed at http://bio-hpc.eu/software/hydroweb/.