Vladimír Horský

ValidatorDB: database of up-to-date validation results for ligands and non-standard residues from the Protein Data Bank

Following the discovery of serious errors in the structure of biomacromolecules, structure validation has become a key topic of research, especially for ligands and non-standard residues. ValidatorDB (freely available at http://ncbr.muni.cz/ValidatorDB) offers a new step in this direction, in the form of a database of validation results for all ligands and non-standard residues from the Protein Data Bank (all molecules with seven or more heavy atoms). Model molecules from the wwPDB Chemical Component Dictionary are used as reference during validation. ValidatorDB covers the main aspects of validation of annotation, and additionally introduces several useful validation analyses. The most significant is the classification of chirality errors, allowing the user to distinguish between serious issues and minor inconsistencies. Other such analyses are able to report, for example, completely erroneous ligands, alternate conformations or complete identity with the model molecules. All results are systematically classified into categories, and statistical evaluations are performed. In addition to detailed validation reports for each molecule, ValidatorDB provides summaries of the validation results for the entire PDB, for sets of molecules sharing the same annotation (three-letter code) or the same PDB entry, and for user-defined selections of annotations or PDB entries.

MotiveValidator: interactive web-based validation of ligand and residue structure in biomolecular complexes

Structure validation has become a major issue in the structural biology community, and an essential step is checking the ligand structure. This paper introduces MotiveValidator, a web-based application for the validation of ligands and residues in PDB or PDBx/mmCIF format files provided by the user. Specifically, MotiveValidator is able to evaluate in a straightforward manner whether the ligand or residue being studied has a correct annotation (3-letter code), i.e. if it has the same topology and stereochemistry as the model ligand or residue with this annotation. If not, MotiveValidator explicitly describes the differences. MotiveValidator offers a user-friendly, interactive and platform-independent environment for validating structures obtained by any type of experiment. The results of the validation are presented in both tabular and graphical form, facilitating their interpretation. MotiveValidator can process thousands of ligands or residues in a single validation run that takes no more than a few minutes. MotiveValidator can be used for testing single structures, or the analysis of large sets of ligands or fragments prepared for binding site analysis, docking or virtual screening. MotiveValidator is freely available via the Internet at http://ncbr.muni.cz/MotiveValidator.

The Eighth Central European Conference “Chemistry towards Biology”: Snapshot

The Eighth Central European Conference “Chemistry towards Biology” was held in Brno, Czech Republic, on August 28–September 1, 2016 to bring together experts in biology, chemistry and design of bioactive compounds; promote the exchange of scientific results, methods and ideas; and encourage cooperation between researchers from all over the world. The topics of the conference covered “Chemistry towards Biology”, meaning that the event welcomed chemists working on biology-related problems, biologists using chemical methods, and students and other researchers of the respective areas that fall within the common scope of chemistry and biology. The authors of this manuscript are plenary speakers and other participants of the symposium and members of their research teams. The following summary highlights the major points/topics of the meeting.

Validation of ligands in macromolecular structures determined by X-ray crystallography

Better metrics are required to be able to assess small-molecule ligands in macromolecular structures in Worldwide Protein Data Bank validation reports. The local ligand density fit (LLDF) score currently used to assess ligand electron-density fit outliers produces a substantial number of false positives and false negatives.

NEEMP: software for validation, accurate calculation and fast parameterization of EEM charges

BackgroundThe concept of partial atomic charges was first applied in physical and organic chemistry and was later also adopted in computational chemistry, bioinformatics and chemoinformatics. The electronegativity equalization method (EEM) is the most frequently used approach for calculating partial atomic charges. EEM is fast and its accuracy is comparable to the quantum mechanical charge calculation method for which it was parameterized. Several EEM parameter sets for various types of molecules and QM charge calculation approaches have been published and new ones are still needed and produced. Methodologies for EEM parameterization have been described in a few articles, but a software tool for EEM parameterization and EEM parameter sets validation has not been available until now.ResultsWe provide the software tool NEEMP (http://ncbr.muni.cz/NEEMP), which offers three main functionalities: EEM parameterization [via linear regression (LR) and differential evolution with local minimization (DE-MIN)]; EEM parameter set validation (i.e., validation of coverage and quality) and EEM charge calculation. NEEMP functionality is shown using a parameterization and a validation case study. The parameterization case study demonstrated that LR is an appropriate approach for smaller and homogeneous datasets and DE-MIN is a suitable solution for larger and heterogeneous datasets. The validation case study showed that EEM parameter set coverage and quality can still be problematic. Therefore, it makes sense to verify the coverage and quality of EEM parameter sets before their use, and NEEMP is an appropriate tool for such verification. Moreover, it seems from both case studies that new EEM parameterizations need to be performed and new EEM parameter sets obtained with high quality and coverage for key structural databases.ConclusionWe provide the software tool NEEMP, which is to the best of our knowledge the only available software package that enables EEM parameterization and EEM parameter set validation. Additionally, its DE-MIN parameterization method is an innovative approach, developed by ourselves and first published in this work. In addition, we also prepared four high-quality EEM parameter sets tailored to ligand molecules.Graphical abstract.