The Eighth Central European Conference "Chemistry towards Biology": snapshot

The Eighth Central European Conference "Chemistry towards Biology" was held in Brno, Czech Republic, on 28 August – 1 September 2016The Eighth Central European Conference "Chemistry towards Biology" was held in Brno, Czech Republic, on 28 August-1 September 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

PDBe: improved findability of macromolecularstructure data in the PDB

© 2019 The Authors. Published by OUP. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/nar/gkz990The Protein Data Bank in Europe (PDBe), a founding member of the Worldwide Protein Data Bank (wwPDB), actively participates in the deposition, curation, validation, archiving and dissemination of macromolecular structure data. PDBe supports diverse research communities in their use of macromolecular structures by enriching the PDB data and by providing advanced tools and services for effective data access, visualization and analysis. This paper details the enrichment of data at PDBe, including mapping of RNA structures to Rfam, and identification of molecules that act as cofactors. PDBe has developed an advanced search facility with ∼100 data categories and sequence searches. New features have been included in the LiteMol viewer at PDBe, with updated visualization of carbohydrates and nucleic acids. Small molecules are now mapped more extensively to external databases and their visual representation has been enhanced. These advances help users to more easily find and interpret macromolecular structure data in order to solve scientific problems.The Protein Data Bank in Europe is supported by European Molecular Biology Laboratory-European Bioinformatics Institute; Wellcome Trust [104948]; Biotechnology and Biological Sciences Research Council [BB/N019172/1, BB/G022577/1, BB/J007471/1, BB/K016970/1, BB/K020013/1, BB/M013146/1, BB/M011674/1, BB/M020347/1, BB/M020428/1, BB/P024351/1]; European Union [284209]; ELIXIR and Open Targets. Funding for open access charge: EMB

PDBe-KB: a community-driven resource for structural and functional annotations.

The Protein Data Bank in Europe-Knowledge Base (PDBe-KB, https://pdbe-kb.org) is a community-driven, collaborative resource for literature-derived, manually curated and computationally predicted structural and functional annotations of macromolecular structure data, contained in the Protein Data Bank (PDB). The goal of PDBe-KB is two-fold: (i) to increase the visibility and reduce the fragmentation of annotations contributed by specialist data resources, and to make these data more findable, accessible, interoperable and reusable (FAIR) and (ii) to place macromolecular structure data in their biological context, thus facilitating their use by the broader scientific community in fundamental and applied research. Here, we describe the guidelines of this collaborative effort, the current status of contributed data, and the PDBe-KB infrastructure, which includes the data exchange format, the deposition system for added value annotations, the distributable database containing the assembled data, and programmatic access endpoints. We also describe a series of novel web-pages-the PDBe-KB aggregated views of structure data-which combine information on macromolecular structures from many PDB entries. We have recently released the first set of pages in this series, which provide an overview of available structural and functional information for a protein of interest, referenced by a UniProtKB accession

Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop.

Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank (PDB) archive, ∼75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery and design, and the goodness-of-fit of ligand models to electron-density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide PDB/Cambridge Crystallographic Data Center/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30-31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the PDB? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated.The workshop was supported by funding to RCSB PDB by the National Science Foundation (DBI 1338415); PDBe by the Wellcome Trust (104948); PDBj by JST-NBDC; BMRB by the National Institute of General Medical Sciences (GM109046); D3R by the National Institute of General Medical Sciences (GM111528); registration fees from industrial participants; and tax-deductible donations to the wwPDB Foundation by the Genentech Foundation and the Bristol-Myers Squibb Foundation.This is the final version of the article. It first appeared from Cell Press via https://doi.org//10.1016/j.str.2016.02.01

Outcome of the First wwPDB/CCDC/D3R Ligand Validation Workshop

Crystallographic studies of ligands bound to biological macromolecules (proteins and nucleic acids) represent an important source of information concerning drug-target interactions, providing atomic level insights into the physical chemistry of complex formation between macromolecules and ligands. Of the more than 115,000 entries extant in the Protein Data Bank (PDB) archive, ∼75% include at least one non-polymeric ligand. Ligand geometrical and stereochemical quality, the suitability of ligand models for in silico drug discovery and design, and the goodness-of-fit of ligand models to electron-density maps vary widely across the archive. We describe the proceedings and conclusions from the first Worldwide PDB/Cambridge Crystallographic Data Center/Drug Design Data Resource (wwPDB/CCDC/D3R) Ligand Validation Workshop held at the Research Collaboratory for Structural Bioinformatics at Rutgers University on July 30–31, 2015. Experts in protein crystallography from academe and industry came together with non-profit and for-profit software providers for crystallography and with experts in computational chemistry and data archiving to discuss and make recommendations on best practices, as framed by a series of questions central to structural studies of macromolecule-ligand complexes. What data concerning bound ligands should be archived in the PDB? How should the ligands be best represented? How should structural models of macromolecule-ligand complexes be validated? What supplementary information should accompany publications of structural studies of biological macromolecules? Consensus recommendations on best practices developed in response to each of these questions are provided, together with some details regarding implementation. Important issues addressed but not resolved at the workshop are also enumerated.This is the publisher’s final pdf. The published article is copyrighted by Elsevier (Cell Press) and can be found at: http://www.cell.com/structure/hom

Electronegativity Equalization Method: Parameterization and Validation for Large Sets of Organic, Organohalogene and Organometal Molecule

The Electronegativity Equalization Method (EEM) is a fast approach for chargecalculation. A challenging part of the EEM is the parameterization, which is performedusing ab initio charges obtained for a set of molecules. The goal of our work was to performthe EEM parameterization for selected sets of organic, organohalogen and organometalmolecules. We have performed the most robust parameterization published so far. The EEMparameterization was based on 12 training sets selected from a database of predicted 3Dstructures (NCI DIS) and from a database of crystallographic structures (CSD). Each setcontained from 2000 to 6000 molecules. We have shown that the number of molecules inthe training set is very important for quality of the parameters. We have improved EEMparameters (STO-3G MPA charges) for elements that were already parameterized,specifically: C, O, N, H, S, F and Cl. The new parameters provide more accurate chargesthan those published previously. We have also developed new parameters for elements thatwere not parameterized yet, specifically for Br, I, Fe and Zn. We have also performedcrossover validation of all obtained parameters using all training sets that included relevantelements and confirmed that calculated parameters provide accurate charges