MOTIVATION: Advances in the prediction of the 3D structures of most known proteins through machine learning have achieved unprecedented accuracies. However, although these computed models are remarkably good, they still challenge accuracy at the atomic level. The Occluded Surface (OS) algorithm is widely used for atomic packing analysis. But it lacks implementations in high-level languages. RESULTS: We introduce FIBOS, an R and Python package incorporating the OS methodology with enhancements. We show how FIBOS can be used to atomically compare experimental structures and AlphaFold predictions. Although the average packing was similar, AlphaFold models exhibited slightly greater variability, revealing a specific pattern of outliers. AVAILABILITY AND IMPLEMENTATION: FIBOS can be installed locally as a PyPi Python or CRAN R package, and it is also available at https://github.com/insilico-unifei/fibos-R and https://github.com/insilico-unifei/fibos-py.

SUMMARY: EasyVS is a web-based platform built to simplify molecule library selection and virtual screening. With an intuitive interface, the tool allows users to go from selecting a protein target with a known structure and tailoring a purchasable molecule library to performing and visualizing docking in a few clicks. Our system also allows users to filter screening libraries based on molecule properties, cluster molecules by similarity and personalize docking parameters. AVAILABILITY AND IMPLEMENTATION: EasyVS is freely available as an easy-to-use web interface at http://biosig.unimelb.edu.au/easyvs. CONTACT: [email protected] or [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Protein-ligand interaction (PLI) networks show how proteins interact with small non-protein ligands through noncovalent bonding. Understanding such interactions is a crucial step towards ligand prediction, target identification and drug design. We propose CALI (Complex network-based Analysis of protein-Ligand Interactions), a graph-based, visual strategy coupled with complex network topological properties to summarize and detect frequent patterns in PLIs. Patterns obtained with CALI were compared to experimentally determined protein-ligand interactions from the CDK2 and Ricin dataset. For the CDK2, CALI found 90% of interacting residues, and all residues of the Ricin that interact with ligands. We devised a powerful visual and interactive strategy to analyze the data, providing a general view of the interaction dataset, showing the most common PLIs from a global perspective.

Interactions between proteins and ligands are relevant in many biological processes. In the last years, such interactions have gained even more attention as the comprehension of protein-ligand molecular recognition is an important step to ligand prediction, target identificantion, and drug design, among others. This article presents GReMLIN (Graph Mining strategy to infer protein-Ligand INteraction patterns), a strategy to search for conserved protein-ligand interactions in a set of related proteins, based on frequent subgraph mining, that is able to perceive structural arrangements relevant for protein-ligand interaction. When compared to experimentally determined interactions, our in silico strategy was able to find many of relevant binding site residues/atoms for CDK2 and active site residues/atoms for Ricin.

UNLABELLED: PDBest (PDB Enhanced Structures Toolkit) is a user-friendly, freely available platform for acquiring, manipulating and normalizing protein structures in a high-throughput and seamless fashion. With an intuitive graphical interface it allows users with no programming background to download and manipulate their files. The platform also exports protocols, enabling users to easily share PDB searching and filtering criteria, enhancing analysis reproducibility. AVAILABILITY AND IMPLEMENTATION: PDBest installation packages are freely available for several platforms at http://www.pdbest.dcc.ufmg.br CONTACT: [email protected], [email protected], [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Receptor-ligand interactions are a central phenomenon in most biological systems. They are characterized by molecular recognition, a complex process mainly driven by physicochemical and structural properties of both receptor and ligand. Understanding and predicting these interactions are major steps towards protein ligand prediction, target identification, lead discovery and drug design. RESULTS: We propose a novel graph-based-binding pocket signature called aCSM, which proved to be efficient and effective in handling large-scale protein ligand prediction tasks. We compare our results with those described in the literature and demonstrate that our algorithm overcomes the competitor's techniques. Finally, we predict novel ligands for proteins from Trypanosoma cruzi, the parasite responsible for Chagas disease, and validate them in silico via a docking protocol, showing the applicability of the method in suggesting ligands for pockets in a real-world scenario. AVAILABILITY AND IMPLEMENTATION: Datasets and the source code are available at http://www.dcc.ufmg.br/∼dpires/acsm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Protein-protein interfaces contain important information about molecular recognition. The discovery of conserved patterns is essential for understanding how substrates and inhibitors are bound and for predicting molecular binding. When an inhibitor binds to different enzymes (e.g. dissimilar sequences, structures or mechanisms what we call cross-inhibition), identification of invariants is a difficult task for which traditional methods may fail. RESULTS: To clarify how cross-inhibition happens, we model the problem, propose and evaluate a methodology called HydroPaCe to detect conserved patterns. Interfaces are modeled as graphs of atomic apolar interactions and hydrophobic patches are computed and summarized by centroids (HP-centroids), and their conservation is detected. Despite sequence and structure dissimilarity, our method achieves an appropriate level of abstraction to obtain invariant properties in cross-inhibition. We show examples in which HP-centroids successfully predicted enzymes that could be inhibited by the studied inhibitors according to BRENDA database. AVAILABILITY: www.dcc.ufmg.br/~raquelcm/hydropace CONTACT: [email protected]; [email protected]; [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.