Improvement of Virtual Screening Predictions using Computational Intelligence Methods

Virtual Screening (VS) methods can considerably aid clinical research, predicting how ligands interact with drug targets. However, the accuracy of most VS methods is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to improve accuracy of scoring functions used in most VS methods we propose a hybrid novel approach where neural networks (NNET) and support vector machines (SVM) methods are trained with databases of known active (drugs) and inactive compounds, this information being exploited afterwards to improve VS predictions.

Improving drug discovery using a neural networks based parallel scoring function

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, but it has been demonstrated that diverse ligands interact with unrelated parts of the target and many VS methods do not take into account this relevant fact. This problem is circumvented by a novel VS methodology named BINDSURF that scans the whole protein surface to find new hotspots, where ligands might potentially interact with, and which is implemented in massively parallel Graphics Processing Units, allowing fast processing of large ligand databases. BINDSURF can thus be used in drug discovery, drug design, drug repurposing and therefore helps considerably in clinical research. However, the accuracy of most VS methods is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to solve this problem, we propose a novel approach where neural networks are trained with databases of known active (drugs) and inactive compounds, and later used to improve VS predictions.

Improving drug discovery using hybrid softcomputing methods

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, but it has been demonstrated that diverse ligands interact with unrelated parts of the target and many VS methods do not take into account this relevant fact. This problem is circumvented by a novel VS methodology named BINDSURF that scans the whole protein surface in order to find new hotspots, where ligands might potentially interact with, and which is implemented in last generation massively parallel GPU hardware, allowing fast processing of large ligand databases. BINDSURF can thus be used in drug discovery, drug design, drug repurposing and therefore helps considerably in clinical research. However, the accuracy of most VS methods and concretely BINDSURF is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to improve accuracy of the scoring functions used in BINDSURF we propose a hybrid novel approach where neural networks (NNET) and support vector machines (SVM) methods are trained with databases of known active (drugs) and inactive compounds, being this information exploited afterwards to improve BINDSURF VS predictions.

Descubrimiento de fármacos basado en cribado virtual refinado con enfoques neuronales paralelos

En el campo de la medicina clínica es crucial poder determinar la seguridad y la eficacia de los fármacos actuales y además acelerar el descubrimiento de nuevos compuestos activos. Para ello se llevan a cabo ensayos de laboratorio, que son métodos muy costosos y que requieren mucho tiempo. Sin embargo, la bioinformática puede facilitar enormemente la investigación clínica para los fines mencionados, ya que proporciona la predicción de la toxicidad de los fármacos y su actividad en enfermedades nuevas, así como la evolución de los compuestos activos descubiertos en ensayos clínicos. Esto se puede lograr gracias a la disponibilidad de herramientas de bioinformática y métodos de cribado virtual por ordenador (CV) que permitan probar todas las hipótesis necesarias antes de realizar los ensayos clínicos, tales como el docking estructural, mediante el programa BINDSURF. Sin embargo, la precisión de la mayoría de los métodos de CV se ve muy restringida a causa de las limitaciones presentes en las funciones de afinidad o scoring que describen las interacciones biomoleculares, e incluso hoy en día estas incertidumbres no se conocen completamente. En este trabajo abordamos este problema, proponiendo un nuevo enfoque en el que las redes neuronales se entrenan con información relativa a bases de datos de compuestos conocidos (proteínas diana y fármacos), y se aprovecha después el método para incrementar la precisión de las predicciones de afinidad del método de CV BINDSURF.

Screening Subclinical Keratoconus With Placido-Based Corneal Indices

Purpose. To assess in a sample of normal, keratoconic, and keratoconus (KC) suspect eyes the performance of a set of new topographic indices computed directly from the digitized images of the Placido rings. Methods. This comparative study was composed of a total of 124 eyes of 106 patients from the ophthalmic clinics Vissum Alicante and Vissum Almería (Spain) divided into three groups: control group (50 eyes), KC group (50 eyes), and KC suspect group (24 eyes). In all cases, a comprehensive examination was performed, including the corneal topography with a Placidobased CSO topography system. Clinical outcomes were compared among groups, along with the discriminating performance of the proposed irregularity indices. Results. Significant differences at level 0.05 were found on the values of the indices among groups by means of Mann-Whitney-Wilcoxon nonparametric test and Fisher exact test. Additional statistical methods, such as receiver operating characteristic analysis and K-fold cross validation, confirmed the capability of the indices to discriminate between the three groups. Conclusions. Direct analysis of the digitized images of the Placido mires projected on the cornea is a valid and effective tool for detection of corneal irregularities. Although based only on the data from the anterior surface of the cornea, the new indices performed well even when applied to the KC suspect eyes. They have the advantage of simplicity of calculation combined with high sensitivity in corneal irregularity detection and thus can be used as supplementary criteria for diagnosing and grading KC that can be added to the current keratometric classifications.