Enumeration of ring-chain tautomers based on SMIRKS rules.

A compound exhibits (prototropic) tautomerism if it can be represented by two or more structures that are related by a formal intramolecular movement of a hydrogen atom from one heavy atom position to another. When the movement of the proton is accompanied by the opening or closing of a ring it is called ring-chain tautomerism. This type of tautomerism is well observed in carbohydrates, but it also occurs in other molecules such as warfarin.

Comparing the Chemical Structure and Protein Content of ChEMBL, DrugBank, Human Metabolome Database and the Therapeutic Target Database.

ChEMBL, DrugBank, Human Metabolome Database and the Therapeutic Target Database are resources of curated chemistry-to-protein relationships widely used in the chemogenomic arena. In this work we have extended an earlier analysis (PMID 22821596) by comparing chemistry and protein target content between 2010 and 2013. For the former, details are presented for overlaps and differences, statistics of stereochemistry as well as stereo representation and MW profiles between the four databases.

QSAR modeling of imbalanced high-throughput screening data in PubChem.

Many of the structures in PubChem are annotated with activities determined in high-throughput screening (HTS) assays. Because of the nature of these assays, the activity data are typically strongly imbalanced, with a small number of active compounds contrasting with a very large number of inactive compounds. We have used several such imbalanced PubChem HTS assays to test and develop strategies to efficiently build robust QSAR models from imbalanced data sets.

A new approach to radial basis function approximation and its application to QSAR.

We describe a novel approach to RBF approximation, which combines two new elements: (1) linear radial basis functions and (2) weighting the model by each descriptor's contribution. Linear radial basis functions allow one to achieve more accurate predictions for diverse data sets. Taking into account the contribution of each descriptor produces more accurate similarity values used for model development.

Computational tools and resources for metabolism-related property predictions. 2. Application to prediction of half-life time in human liver microsomes.

Background: The most important factor affecting metabolic excretion of compounds from the body is their half-life time. This provides an indication of compound stability of, for example, drug molecules. We report on our efforts to develop QSAR models for metabolic stability of compounds, based on in vitro half-life assay data measured in human liver microsomes.

Mapping between databases of compounds and protein targets.

Databases that provide links between bioactive compounds and their protein targets are increasingly important in drug discovery and chemical biology. They join the expanding universes of cheminformatics via chemical structures on the one hand and bioinformatics via sequences on the other. However, it is difficult to assess the relative utility of databases without the explicit comparison of content.

PDB ligand conformational energies calculated quantum-mechanically.

We present here a greatly updated version of an earlier study on the conformational energies of protein-ligand complexes in the Protein Data Bank (PDB) [Nicklaus et al. Bioorg. Med.

Software and resources for computational medicinal chemistry.

Computer-aided drug design plays a vital role in drug discovery and development and has become an indispensable tool in the pharmaceutical industry. Computational medicinal chemists can take advantage of all kinds of software and resources in the computer-aided drug design field for the purposes of discovering and optimizing biologically active compounds. This article reviews software and other resources related to computer-aided drug design approaches, putting particular emphasis on structure-based drug design, ligand-based drug design, chemical databases and chemoinformatics tools.

Tautomerism in large databases.

We have used the Chemical Structure DataBase (CSDB) of the NCI CADD Group, an aggregated collection of over 150 small-molecule databases totaling 103.5 million structure records, to conduct tautomerism analyses on one of the largest currently existing sets of real (i.e.