Combinatorial Chemistry & High Throughput Screening - Volume 14, Issue 6, 2011

In the early days of combinatorial chemistry, molecular diversity was the most important property to be considered for its application in drug discovery. Over the years, it was also realized that enrichment of chemical libraries with molecules of interest for particular targets could be another way to evolve compounds into realistic drug candidates. Thus, interest in library design has shifted towards the generation of th Read More

Due to the huge amount of data generated in drug discovery programs, their success strongly depends on both the workflows and platforms to manage and, more importantly, to integrate different chemical and biological data sources. At Experimental Therapeutics Program in the Spanish National Cancer Research Center (CNIO), we have addressed our efforts in the design and optimal implementation of those key process Read More

Quantitative structure-activity relationships (QSARs) have important applications in drug discovery research, environmental fate modeling, property prediction, etc. Validation has been recognized as a very important step for QSAR model development. As one of the important objectives of QSAR modeling is to predict activity/property/toxicity of new chemicals falling within the domain of applicability of the developed models and Q Read More

Virtual screening is increasingly being used in drug discovery programs with a growing number of successful applications. Experimental methodologies developed to speed up the drug discovery processes include high throughput screening and combinatorial chemistry. The complementarities between computational and experimental screenings have been recognized and reviewed in the literature. Computa Read More

A pharmacophore is a model which represents the key physico-chemical interactions that mediate biological activity. There is a long history of using pharmacophore modeling methods to select subsets of compounds, focused towards a specific target of interest. This paper will review existing computational methods for deriving and comparing pharmacophore models. We outline a new classification of pharmacophore method Read More

Fragment-based screening is an emerging technology which is used as an alternative to high-throughput screening (HTS), and often in parallel. Fragment screening focuses on very small compounds. Because of their small size and simplicity, fragments exhibit a low to medium binding affinity (mM to μM) and must therefore be screened at high concentration in order to detect binding events. Since some issues are asso Read More

Target-focused compound libraries are collections of compounds which are designed to interact with an individual protein target or, frequently, a family of related targets (such as kinases, voltage-gated ion channels, serine/cysteine proteases). They are used for screening against therapeutic targets in order to find hit compounds that might be further developed into drugs. The design of such libraries generally utilizes structur Read More

The goal of computational protein structure prediction is to provide three-dimensional (3D) structures with resolution comparable to experimental results. Comparative modeling, which predicts the 3D structure of a protein based on its sequence similarity to homologous structures, is the most accurate computational method for structure prediction. In the last two decades, significant progress has been made on comparative m Read More

Chemoinformatics is a scientific discipline at the interface between chemistry and computer science, which nowadays is currently implemented in pharmaceutical companies as a part of the usual drug discovery pathway. Furthermore, taking into account the vast amount of experimental and computational data currently generated on drug discovery projects, the use of chemoinformatics tools has become increasingly necess Read More

Rafael Gozalbes holds a Ph.D. in Physical Chemistry from the University of Valencia, Spain (1998). After a post-doctoral position at the “Groupe de Chimie Informatique et Modelisation” (ITODYS) and Faculte de Medecine, both at the Universite Paris VII, he spent seven years as senior scientist at the Modelling group of CEREP, a biotech company, in France. Since 2007 he is scientific collaborator at the Structural Biochemistry Labo Read More