Articles

A visual approach for analysis and inference of molecular activity spaces

Molecular space visualization can help to explore the diversity of large heterogeneous chemical data, which ultimately may increase the understanding of structure-activity relationships (SAR) in drug discovery...

Authors: Samina Kausar and Andre O. Falcao

A path to next-generation reproducibility in cheminformatics

Currently, the submission guidelines for the Journal of Cheminformatics say it will “only publish research or software that is entirely reproducible by third parties.” They go on to specify that being reproduc...

Authors: Robert D. Clark

A general approach for retrosynthetic molecular core analysis

Scaffold analysis of compound data sets has reemerged as a chemically interpretable alternative to machine learning for chemical space and structure–activity relationships analysis. In this context, analog ser...

Authors: J. Jesús Naveja, B. Angélica Pilón-Jiménez, Jürgen Bajorath and José L. Medina-Franco

Open-source QSAR models for pKa prediction using multiple machine learning approaches

The logarithmic acid dissociation constant pKa reflects the ionization of a chemical, which affects lipophilicity, solubility, protein binding, and ability to pass through the plasma membrane. Thus, pKa affect...

Authors: Kamel Mansouri, Neal F. Cariello, Alexandru Korotcov, Valery Tkachenko, Chris M. Grulke, Catherine S. Sprankle, David Allen, Warren M. Casey, Nicole C. Kleinstreuer and Antony J. Williams

Machine learning models for hydrogen bond donor and acceptor strengths using large and diverse training data generated by first-principles interaction free energies

We present machine learning (ML) models for hydrogen bond acceptor (HBA) and hydrogen bond donor (HBD) strengths. Quantum chemical (QC) free energies in solution for 1:1 hydrogen-bonded complex formation to th...

Authors: Christoph A. Bauer, Gisbert Schneider and Andreas H. Göller

SAR and QSAR modeling of a large collection of LD₅₀ rat acute oral toxicity data

The median lethal dose for rodent oral acute toxicity (LD50) is a standard piece of information required to categorize chemicals in terms of the potential hazard posed to human health after acute exposure. The...

Authors: Domenico Gadaleta, Kristijan Vuković, Cosimo Toma, Giovanna J. Lavado, Agnes L. Karmaus, Kamel Mansouri, Nicole C. Kleinstreuer, Emilio Benfenati and Alessandra Roncaglioni

Flexible heuristic algorithm for automatic molecule fragmentation: application to the UNIFAC group contribution model

A priori calculation of thermophysical properties and predictive thermodynamic models can be very helpful for developing new industrial processes. Group contribution methods link the target property to contrib...

Authors: Simon Müller

PUG-View: programmatic access to chemical annotations integrated in PubChem

PubChem is a chemical data repository that provides comprehensive information on various chemical entities. It contains a wealth of chemical information from hundreds of data sources. Programmatic access to th...

Authors: Sunghwan Kim, Paul A. Thiessen, Tiejun Cheng, Jian Zhang, Asta Gindulyte and Evan E. Bolton

NaPLeS: a natural products likeness scorer—web application and database

Natural products (NPs), often also referred to as secondary metabolites, are small molecules synthesised by living organisms. Natural products are of interest due to their bioactivity and in this context as st...

Authors: Maria Sorokina and Christoph Steinbeck

Combining structural and bioactivity-based fingerprints improves prediction performance and scaffold hopping capability

This study aims at improving upon existing activity predictions methods by augmenting chemical structure fingerprints with bio-activity based fingerprints derived from high-throughput screening (HTS) data (HTS...

Authors: Oliver Laufkötter, Noé Sturm, Jürgen Bajorath, Hongming Chen and Ola Engkvist

Accuracy evaluation and addition of improved dihedral parameters for the MMFF94s

The Platinum dataset of protein-bound ligand conformations was used to benchmark the ability of the MMFF94s force field to generate bioactive conformations by minimization of randomly generated conformers. Tor...

Authors: Joel Wahl, Joel Freyss, Modest von Korff and Thomas Sander

DLIGAND2: an improved knowledge-based energy function for protein–ligand interactions using the distance-scaled, finite, ideal-gas reference state

Performance of structure-based molecular docking largely depends on the accuracy of scoring functions. One important type of scoring functions are knowledge-based potentials derived from known three-dimensiona...

Authors: Pin Chen, Yaobin Ke, Yutong Lu, Yunfei Du, Jiahui Li, Hui Yan, Huiying Zhao, Yaoqi Zhou and Yuedong Yang

Correction to: A new topological descriptor for water network structure

It was highlighted that the original article [1] was missing Additional files 2 and 3.

Authors: Lee Steinberg, John Russo and Jeremy Frey

Rapid prediction of NMR spectral properties with quantified uncertainty

Accurate calculation of specific spectral properties for NMR is an important step for molecular structure elucidation. Here we report the development of a novel machine learning technique for accurately predic...

Authors: Eric Jonas and Stefan Kuhn

Fast, efficient fragment-based coordinate generation for Open Babel

Rapidly predicting an accurate three dimensional geometry of a molecule is a crucial task for cheminformatics and across a wide range of molecular modeling. Consequently, developing a fast, accurate, and open ...

Authors: Naruki Yoshikawa and Geoffrey R. Hutchison

A new topological descriptor for water network structure

Bulk water molecular dynamics simulations based on a series of atomistic water potentials (TIP3P, TIP4P/Ew, SPC/E and OPC) are compared using new techniques from the field of topological data analysis. The top...

Authors: Lee Steinberg, John Russo and Jeremy Frey

Bioactivity-explorer: a web application for interactive visualization and exploration of bioactivity data

To better leverage the accumulated bioactivity data in the ChEMBL database, we have developed Bioactivity-explorer, a web application for interactive visualization and exploration of the large-scale bioactivit...

Authors: Lu Liang, Chunfeng Ma, Tengfei Du, Yufei Zhao, Xiaoyong Zhao, Mengmeng Liu, Zhonghua Wang and Jianping Lin

Multi-channel PINN: investigating scalable and transferable neural networks for drug discovery

Analysis of compound–protein interactions (CPIs) has become a crucial prerequisite for drug discovery and drug repositioning. In vitro experiments are commonly used in identifying CPIs, but it is not feasible ...

Authors: Munhwan Lee, Hyeyeon Kim, Hyunwhan Joe and Hong-Gee Kim

Journal of Cheminformatics, ORCID, and GitHub

Authors: Egon Willighagen, Nina Jeliazkova and Rajarshi Guha

Interoperable chemical structure search service

The existing connections between large databases of chemicals, proteins, metabolites and assays offer valuable resources for research in fields ranging from drug design to metabolomics. Transparent search acro...

Authors: Miroslav Kratochvíl, Jiří Vondrášek and Jakub Galgonek

Cheminformatics approach to exploring and modeling trait-associated metabolite profiles

Developing predictive and transparent approaches to the analysis of metabolite profiles across patient cohorts is of critical importance for understanding the events that trigger or modulate traits of interest...

Authors: Jeremy R. Ash, Melaine A. Kuenemann, Daniel Rotroff, Alison Motsinger-Reif and Denis Fourches

Next generation community assessment of biomedical entity recognition web servers: metrics, performance, interoperability aspects of BeCalm

Shared tasks and community challenges represent key instruments to promote research, collaboration and determine the state of the art of biomedical and chemical text mining technologies. Traditionally, such ta...

Authors: Martin Pérez-Pérez, Gael Pérez-Rodríguez, Aitor Blanco-Míguez, Florentino Fdez-Riverola, Alfonso Valencia, Martin Krallinger and Anália Lourenço

KekuleScope: prediction of cancer cell line sensitivity and compound potency using convolutional neural networks trained on compound images

The application of convolutional neural networks (ConvNets) to harness high-content screening images or 2D compound representations is gaining increasing attention in drug discovery. However, existing applicat...

Authors: Isidro Cortés-Ciriano and Andreas Bender

DockRMSD: an open-source tool for atom mapping and RMSD calculation of symmetric molecules through graph isomorphism

Comparison of ligand poses generated by protein–ligand docking programs has often been carried out with the assumption of direct atomic correspondence between ligand structures. However, this correspondence is...

Authors: Eric W. Bell and Yang Zhang

Improved algorithms for quantifying the near symmetry of proteins: complete side chains analysis

Symmetry of proteins, an important source of their elegant structure and unique functions, is not as perfect as it may seem. In the framework of continuous symmetry, in which symmetry is no longer a binary yes...

Authors: Inbal Tuvi-Arad and Gil Alon

An integrated quantitative structure and mechanism of action-activity relationship model of human serum albumin binding

Traditional quantitative structure-activity relationship models usually neglect the molecular alterations happening in the exposed systems (the mechanism of action, MOA), that mediate between structural proper...

Authors: Angela Serra, Serli Önlü, Pietro Coretto and Dario Greco

ErtlFunctionalGroupsFinder: automated rule-based functional group detection with the Chemistry Development Kit (CDK)

The Ertl algorithm for automated functional groups (FG) detection and extraction of organic molecules is implemented on the basis of the Chemistry Development Kit (CDK). A distinct impact of the chosen CDK aro...

Authors: Sebastian Fritsch, Stefan Neumann, Jonas Schaub, Christoph Steinbeck and Achim Zielesny

Leveraging heterogeneous data from GHS toxicity annotations, molecular and protein target descriptors and Tox21 assay readouts to predict and rationalise acute toxicity

Despite the increasing knowledge in both the chemical and biological domains the assimilation and exploration of heterogeneous datasets, encoding information about the chemical, bioactivity and phenotypic prop...

Authors: Chad H. G. Allen, Lewis H. Mervin, Samar Y. Mahmoud and Andreas Bender

An exploration strategy improves the diversity of de novo ligands using deep reinforcement learning: a case for the adenosine A_2A receptor

Over the last 5 years deep learning has progressed tremendously in both image recognition and natural language processing. Now it is increasingly applied to other data rich fields. In drug discovery, recurrent...

Authors: Xuhan Liu, Kai Ye, Herman W. T. van Vlijmen, Adriaan P. IJzerman and Gerard J. P. van Westen

Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening

Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library pr...

Authors: Patrick J. Ropp, Jacob O. Spiegel, Jennifer L. Walker, Harrison Green, Guillermo A. Morales, Katherine A. Milliken, John J. Ringe and Jacob D. Durrant

Capturing mixture composition: an open machine-readable format for representing mixed substances

We describe a file format that is designed to represent mixtures of compounds in a way that is fully machine readable. This Mixfile format is intended to fill the same role for substances that are composed of mul...

Authors: Alex M. Clark, Leah R. McEwen, Peter Gedeck and Barry A. Bunin

Bayesian optimization for conformer generation

Generating low-energy molecular conformers is a key task for many areas of computational chemistry, molecular modeling and cheminformatics. Most current conformer generation methods primarily focus on generati...

Authors: Lucian Chan, Geoffrey R. Hutchison and Garrett M. Morris

Correction to: A new semi-automated workflow for chemical data retrieval and quality checking for modeling applications

It was highlighted that the original article [1] contained an error in the Funding section. This Correction article states the correct and incorrect versions of the Funding section.

Authors: Domenico Gadaleta, Anna Lombardo, Cosimo Toma and Emilio Benfenati

DNAmod: the DNA modification database

Covalent DNA modifications, such as 5-methylcytosine (5mC), are increasingly the focus of numerous research programs. In eukaryotes, both 5mC and 5-hydroxymethylcytosine (5hmC) are now recognized as stable epi...

Authors: Ankur Jai Sood, Coby Viner and Michael M. Hoffman

TeachOpenCADD: a teaching platform for computer-aided drug design using open source packages and data

Owing to the increase in freely available software and data for cheminformatics and structural bioinformatics, research for computer-aided drug design (CADD) is more and more built on modular, reproducible, an...

Authors: Dominique Sydow, Andrea Morger, Maximilian Driller and Andrea Volkamer

Detecting drug communities and predicting comprehensive drug–drug interactions via balance regularized semi-nonnegative matrix factorization

Because drug–drug interactions (DDIs) may cause adverse drug reactions or contribute to complex-disease treatments, it is important to identify DDIs before multiple-drug medications are prescribed. As the alte...

Authors: Jian-Yu Shi, Kui-Tao Mao, Hui Yu and Siu-Ming Yiu

Methodology of aiQSAR: a group-specific approach to QSAR modelling

Several QSAR methodology developments have shown promise in recent years. These include the consensus approach to generate the final prediction of a model, utilizing new, advanced machine learning algorithms a...

Authors: Kristijan Vukovic, Domenico Gadaleta and Emilio Benfenati

QligFEP: an automated workflow for small molecule free energy calculations in Q

The process of ligand binding to a biological target can be represented as the equilibrium between the relevant solvated and bound states of the ligand. This which is the basis of structure-based, rigorous met...

Authors: Willem Jespers, Mauricio Esguerra, Johan Åqvist and Hugo Gutiérrez-de-Terán

Algorithm-supported, mass and sequence diversity-oriented random peptide library design

Random peptide libraries that cover large search spaces are often used for the discovery of new binders, even when the target is unknown. To ensure an accurate population representation, there is a tendency to...

Authors: Daniela Kalafatovic, Goran Mauša, Toni Todorovski and Ernest Giralt

Binding mode information improves fragment docking

Docking is commonly used in drug discovery to predict how ligand binds to protein target. Best programs are generally able to generate a correct solution, yet often fail to identify it. In the case of drug-lik...

Authors: Célien Jacquemard, Malgorzata N. Drwal, Jérémy Desaphy and Esther Kellenberger

Too many tags spoil the metadata: investigating the knowledge management of scientific research with semantic web technologies

Scientific research is increasingly characterised by the volume of documents and data that it produces, from experimental plans and raw data to reports and papers. Researchers frequently struggle to manage and...

Authors: Samantha Kanza, Nicholas Gibbins and Jeremy G. Frey

KMR: knowledge-oriented medicine representation learning for drug–drug interaction and similarity computation

Efficient representations of drugs provide important support for healthcare analytics, such as drug–drug interaction (DDI) prediction and drug–drug similarity (DDS) computation. However, incomplete annotated d...

Authors: Ying Shen, Kaiqi Yuan, Min Yang, Buzhou Tang, Yaliang Li, Nan Du and Kai Lei

CRFVoter: gene and protein related object recognition using a conglomerate of CRF-based tools

Gene and protein related objects are an important class of entities in biomedical research, whose identification and extraction from scientific articles is attracting increasing interest. In this work, we desc...

Authors: Wahed Hemati and Alexander Mehler

Exploring the GDB-13 chemical space using deep generative models

Recent applications of recurrent neural networks (RNN) enable training models that sample the chemical space. In this study we train RNN with molecular string representations (SMILES) with a subset of the enum...

Authors: Josep Arús-Pous, Thomas Blaschke, Silas Ulander, Jean-Louis Reymond, Hongming Chen and Ola Engkvist

Design, implementation, and operation of a rapid, robust named entity recognition web service

Most BioCreative tasks to date have focused on assessing the quality of text-mining annotations in terms of precision and recall. Interoperability, speed, and stability are, however, other important factors to...

Authors: Sune Pletscher-Frankild and Lars Juhl Jensen

Automated simultaneous assignment of bond orders and formal charges

Bond orders and formal charges are fundamental chemical descriptors. In cheminformatic applications it is necessary to be able to assign these properties to a given molecular structure automatically, given min...

Authors: Ivan D. Welsh and Jane R. Allison

CSgator: an integrated web platform for compound set analysis

Drug discovery typically involves investigation of a set of compounds (e.g. drug screening hits) in terms of target, disease, and bioactivity. CSgator is a comprehensive analytic tool for set-wise interpretati...

Authors: Sera Park, Yeajee Kwon, Hyesoo Jung, Sukyung Jang, Haeseung Lee and Wankyu Kim

Software solutions for evaluation and visualization of laser ablation inductively coupled plasma mass spectrometry imaging (LA-ICP-MSI) data: a short overview

Mass spectrometry imaging (MSI) using laser ablation (LA) inductively coupled plasma (ICP) is an innovative and exciting methodology to perform highly sensitive elemental analyses. LA-ICP-MSI of metals, trace ...

Authors: Ralf Weiskirchen, Sabine Weiskirchen, Philipp Kim and Robert Winkler

Identification of novel small molecule inhibitors for solute carrier SGLT1 using proteochemometric modeling

Sodium-dependent glucose co-transporter 1 (SGLT1) is a solute carrier responsible for active glucose absorption. SGLT1 is present in both the renal tubules and small intestine. In contrast, the closely related...

Authors: Lindsey Burggraaff, Paul Oranje, Robin Gouka, Pieter van der Pijl, Marian Geldof, Herman W. T. van Vlijmen, Adriaan P. IJzerman and Gerard J. P. van Westen

Dimorphite-DL: an open-source program for enumerating the ionization states of drug-like small molecules

Small-molecule protonation can promote or discourage protein binding by altering hydrogen-bond, electrostatic, and van-der-Waals interactions. To improve virtual-screen pose and affinity predictions, researche...

Authors: Patrick J. Ropp, Jesse C. Kaminsky, Sara Yablonski and Jacob D. Durrant