MOTIVATION: Popular shape-based alignment methods handle molecular flexibility by utilizing conformational ensembles to select the most fitted conformer. However, the initial conformer library generation step is computationally intensive and limiting to the overall alignment process. In this work, we describe a method to perform flexible alignment of two molecular shapes by optimizing the 3D conformation. SENSAAS-Flex, an add-on to the SENSAAS tool, is able to proceed from a limited set of initial conformers through an iterative process where additional conformational optimizations are made at the substructure level and constrained by the target shape. RESULTS: In self- and cross-alignment experiments, SENSAAS-Flex is able to reproduce the crystal structure geometry of ligands of the AstraZeneca Molecule Overlay Test set and PDBbind refined dataset. Our study shows that the point-based representation of molecular surfaces is appropriate in terms of shape constraint to sample the conformational space and perform flexible molecular alignments. AVAILABILITY AND IMPLEMENTATION: The documentation and source code are available at https://chemoinfo.ipmc.cnrs.fr/Sensaas-flex/sensaas-flex-main.tar.gz.

Abstract Motivation: In the drug discovery field, new uses for old drugs, selective optimization of side activities and fragment-based drug design (FBDD) have proved to be successful alternatives to high-throughput screening. e-Drug3D is a database of 3D chemical structures of drugs that provides several collections of ready-to-screen SD files of drugs and commercial drug fragments. They are natural inputs in studies dedicated to drug repurposing and FBDD. Availability: e-Drug3D collections are freely available at http://chemoinfo.ipmc.cnrs.fr/e-drug3d.html either for download or for direct in silico web-based screenings. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online.

SUMMARY: HELIQUEST calculates the physicochemical properties and amino acid composition of an alpha-helix and screens databank to identify protein segments possessing similar features. This server is also dedicated to mutating helices manually or automatically by genetic algorithm to design analogues of defined features. AVAILABILITY: http://heliquest.ipmc.cnrs.fr.

MOTIVATION: Public resources for studying protein interfaces are necessary for better understanding of molecular recognition and developing intermolecular potentials, search procedures and scoring functions for the prediction of protein complexes. RESULTS: The first release of the DOCKGROUND resource implements a comprehensive database of co-crystallized (bound-bound) protein-protein complexes, providing foundation for the upcoming expansion to unbound (experimental and simulated) protein-protein complexes, modeled protein-protein complexes and systematic sets of docking decoys. The bound-bound part of DOCKGROUND is a relational database of annotated structures based on the Biological Unit file (Biounit) provided by the RCSB as a separated file containing probable biological molecule. DOCKGROUND is automatically updated to reflect the growth of PDB. It contains 67,220 pairwise complexes that rely on 14,913 Biounit entries from 34,778 PDB entries (January 30, 2006). The database includes a dynamic generation of non-redundant datasets of pairwise complexes based either on the structural similarity (SCOP classification) or on user-defined sequence identity. The growing DOCKGROUND resource is designed to become a comprehensive public environment for developing and validating new methodologies for modeling of protein interactions. AVAILABILITY: DOCKGROUND is available at http://dockground.bioinformatics.ku.edu. The current first release implements the bound-bound part.

UNLABELLED: We have developed a WWW server for the integration and comparison of protein structure predictions performed by five different servers. Users submit an amino acid sequence to a selected set of these prediction methods. Results are gathered on a web-based page in order to facilitate comparison and analysis. All the alignments are further evaluated through a common threading tool making their comparisons easier. AVAILABILITY: The meta-server is available free at http://www.infobiosud.cnrs.fr/bioserver SUPPLEMENTARY INFORMATION: http://www.infobiosud.cnrs.fr/bioserver/hah1.html