Landscape of In Silico Tools for Modeling Covalent Modification of Proteins: A Review on Computational Covalent Drug Discovery

BIreactive: Expanding the Scope of Reactivity Predictions to Propynamides

(2023) Markus R. Hermann et al.   Pharmaceuticals

Benchmarking In Silico Tools for Cysteine pKa Prediction

(2023) Ernest Awoonor-Williams et al.   Journal of Chemical Information and Modeling

To Design Scalable Free Energy Perturbation Networks, Optimal Is Not Enough

(2023) Mary Pitman et al.   Journal of Chemical Information and Modeling

Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases

(2023) Aarion Romany et al.   Journal of Chemical Information and Modeling

Integrated Covalent Drug Design Workflow Using Site Identification by Ligand Competitive Saturation

(2023) Wenbo Yu et al.   Journal of Chemical Theory and Computation

Discovery of a New-Generation S-Adenosylmethionine-Noncompetitive Covalent Inhibitor Targeting the Lysine Methyltransferase Enhancer of Zeste Homologue 2

(2023) Yi Zhang et al.   Journal of Medicinal Chemistry

Mathematical Model for Covalent Proteolysis Targeting Chimeras: Thermodynamics and Kinetics Underlying Catalytic Efficiency

(2023) Charu Chaudhry   Journal of Medicinal Chemistry

Data-Driven Global Assessment of Protein Kinase Inhibitors with Emphasis on Covalent Compounds

(2023) Elena Xerxa et al.   Journal of Medicinal Chemistry

Potent and selective covalent inhibition of the papain-like protease from SARS-CoV-2

(2023) Brian C. Sanders et al.   Nature Communications

Quantum Chemistry–Machine Learning Approach for Predicting Properties of Lewis Acid–Lewis Base Adducts

(2023) Hieu Huynh et al.   ACS Omega

Covalent allosteric inhibitors of Akt generated using a click fragment approach

(2022) Leandi van der Westhuizen et al.   ChemMedChem

Mechanistic Modeling of Monoglyceride Lipase Covalent Modification Elucidates the Role of Leaving Group Expulsion and Discriminates Inhibitors with High and Low Potency

(2022) Francesca Galvani et al.   Journal of Chemical Information and Modeling

SAMPL7 protein-ligand challenge: A community-wide evaluation of computational methods against fragment screening and pose-prediction

(2022) Harold Grosjean et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

The Ascension of Targeted Covalent Inhibitors

(2022) Juswinder Singh   JOURNAL OF MEDICINAL CHEMISTRY

Cov_DOX: A Method for Structure Prediction of Covalent Protein–Ligand Bindings

(2022) Lin Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

Progress and Challenges in Targeting the SARS-CoV-2 Papain-like Protease

(2022) Haozhou Tan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fast and Effective Prediction of the Absolute Binding Free Energies of Covalent Inhibitors of SARS-CoV-2 Main Protease and 20S Proteasome

(2022) Jiao Zhou et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AI-Aided Design of Novel Targeted Covalent Inhibitors against SARS-CoV-2

(2022) Bowen Tang et al.   Biomolecules

Informing geometric deep learning with electronic interactions to accelerate quantum chemistry

(2022) Zhuoran Qiao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Absolute binding free energy calculations improve enrichment of actives in virtual compound screening

(2022) Mudong Feng et al.   Scientific Reports

Mechanistic Investigation of Lysine-Targeted Covalent Inhibition of PI3Kδ via ONIOM QM:QM Computations

(2022) Volkan Fındık et al.   Journal of Chemical Information and Modeling

Assessment of Reversibility for Covalent Cysteine Protease Inhibitors Using Quantum Mechanics/Molecular Mechanics Free Energy Surfaces

(2022) Alberto M. Dos Santos et al.   Journal of Chemical Information and Modeling

Docking covalent targets for drug discovery: stimulating the computer-aided drug design community of possible pitfalls and erroneous practices

(2022) Abdul-Quddus Kehinde Oyedele et al.   MOLECULAR DIVERSITY

Targeting SARS-CoV-2 papain-like protease in the postvaccine era

(2022) Anh-Tien Ton et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Glycoside Hydrolase Catalysis: Do Substrates and Mechanism-Based Covalent Inhibitors React via Matching Transition States?

(2022) Oluwafemi Akintola et al.   ACS Catalysis

WIDOCK: a reactive docking protocol for virtual screening of covalent inhibitors

(2021) Andrea Scarpino et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Automation of absolute protein-ligand binding free energy calculations for docking refinement and compound evaluation

(2021) Germano Heinzelmann et al.   Scientific Reports

Electrostatically embedded m olecules‐in‐molecules approach and its application to molecular clusters

(2021) Vikrant Tripathy et al.   JOURNAL OF COMPUTATIONAL CHEMISTRY

Identification of ebselen and its analogues as potent covalent inhibitors of papain-like protease from SARS-CoV-2

(2021) Ewelina Weglarz-Tomczak et al.   Scientific Reports

Challenges Encountered Applying Equilibrium and Nonequilibrium Binding Free Energy Calculations

(2021) Hannah M. Baumann et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Predicting the Relative Binding Affinity for Reversible Covalent Inhibitors by Free Energy Perturbation Calculations

(2021) Vinícius Bonatto et al.   Journal of Chemical Information and Modeling

Modeling the Binding and Conformational Energetics of a Targeted Covalent Inhibitor to Bruton’s Tyrosine Kinase

(2021) Ernest Awoonor-Williams et al.   Journal of Chemical Information and Modeling

Impact of Warhead Modulations on the Covalent Inhibition of SARS-CoV-2 Mpro Explored by QM/MM Simulations

(2021) Sergio Martí et al.   ACS Catalysis

Evaluating QM/MM Free Energy Surfaces for Ranking Cysteine Protease Covalent Inhibitors

(2020) Clauber H. S. da Costa et al.   Journal of Chemical Information and Modeling

ON THE ASSESSMENT OF THE CRUZAIN CYSTEINE PROTEASE REVERSIBLE AND IRREVERSIBLE COVALENT INHIBITION MECHANISM

(2020) José Rogério A. Silva et al.   Journal of Chemical Information and Modeling

Cov_FB3D: A De Novo Covalent Drug Design Protocol Integrating the BA-SAMP Strategy and Machine-Learning-Based Synthetic Tractability Evaluation

(2020) Lin Wei et al.   Journal of Chemical Information and Modeling

BIreactive: A Machine-Learning Model to Estimate Covalent Warhead Reactivity

(2020) Ferruccio Palazzesi et al.   Journal of Chemical Information and Modeling

SuFEx-enabled high-throughput medicinal chemistry

(2020) Seiya Kitamura et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors

(2020) Linlin Zhang et al.   SCIENCE

Exploring the Proteolysis Mechanism of the Proteasomes

(2020) Arjun Saha et al.   JOURNAL OF PHYSICAL CHEMISTRY B

OrbNet: Deep learning for quantum chemistry using symmetry-adapted atomic-orbital features

(2020) Zhuoran Qiao et al.   JOURNAL OF CHEMICAL PHYSICS

Machine learning-accelerated quantum mechanics-based atomistic simulations for industrial applications

(2020) Tobias Morawietz et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19

(2020) Robert L. Hoffman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Exploring the Mechanism of Covalent Inhibition: Simulating the Binding Free Energy of α-Ketoamide Inhibitors of the Main Protease of SARS-CoV-2

(2020) Dibyendu Mondal et al.   BIOCHEMISTRY

Affinity and Selectivity Assessment of Covalent Inhibitors by Free Energy Calculations

(2020) Levente M. Mihalovits et al.   Journal of Chemical Information and Modeling

Exploring the Catalytic Reaction of Cysteine Proteases

(2020) Gabriel Oanca et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Ranking Reversible Covalent Drugs: From Free Energy Perturbation to Fragment Docking

(2019) Han Zhang et al.   Journal of Chemical Information and Modeling

Conformation search across multiple-level potential-energy- surfaces (CSAMP): A strategy for accurate prediction of protein-ligand binding structures

(2019) Lin Wei et al.   Journal of Chemical Theory and Computation

Systematic Studies on the Protocol and Criteria for Selecting a Covalent Docking Tool

(2019) Chang Wen et al.   MOLECULES

Toward Atomistic Modeling of Irreversible Covalent Inhibitor Binding Kinetics

(2019) Haoyu S. Yu et al.   Journal of Chemical Information and Modeling

Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix

(2019) Dorothee Liebschner et al.   Acta Crystallographica Section D-Structural Biology

Quantum mechanics/molecular mechanics studies of the mechanism of cysteine proteases inhibition by dipeptidyl nitroalkenes

(2019) Vicent Moliner et al.   CHEMISTRY-A EUROPEAN JOURNAL

Ensemble Docking in Drug Discovery

(2018) Rommie E. Amaro et al.   BIOPHYSICAL JOURNAL

Structure-based design of targeted covalent inhibitors

(2018) Richard Lonsdale et al.   CHEMICAL SOCIETY REVIEWS

Comparative Evaluation of Covalent Docking Tools

(2018) Andrea Scarpino et al.   Journal of Chemical Information and Modeling

Experimental study and computational modelling of cruzain cysteine protease inhibition by dipeptidyl nitriles

(2018) Alberto Monteiro Dos Santos et al.   PHYSICAL CHEMISTRY CHEMICAL PHYSICS

Genetic and Modifiable Risk Factors Contributing to Cisplatin-induced Toxicities

(2018) Matthew R. Trendowski et al.   CLINICAL CANCER RESEARCH

Predicting the Binding of Fatty Acid Amide Hydrolase Inhibitors by Free Energy Perturbation

(2018) Arjun Saha et al.   Journal of Chemical Theory and Computation

Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology

(2018) Matthias Gehringer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Expanding the Armory: Predicting and Tuning Covalent Warhead Reactivity

(2017) Richard Lonsdale et al.   Journal of Chemical Information and Modeling

Can Relative Binding Free Energy Predict Selectivity of Reversible Covalent Inhibitors?

(2017) Payal Chatterjee et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Redox-based reagents for chemoselective methionine bioconjugation

(2017) Shixian Lin et al.   SCIENCE

Computational Study of the Catalytic Mechanism of the Cruzain Cysteine Protease

(2017) Kemel Arafet et al.   ACS Catalysis

Controlling Allosteric Networks in Proteins

(2016) Nikolay V. Dokholyan   CHEMICAL REVIEWS

Emerging Computational Methods for the Rational Discovery of Allosteric Drugs

(2016) Jeffrey R. Wagner et al.   CHEMICAL REVIEWS

Targeting biomolecules with reversible covalent chemistry

(2016) Anupam Bandyopadhyay et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Kinetics and Thermodynamics of Reversible Thiol Additions to Mono- and Diactivated Michael Acceptors: Implications for the Design of Drugs That Bind Covalently to Cysteines

(2016) Elizabeth H. Krenske et al.   JOURNAL OF ORGANIC CHEMISTRY

Quantum Chemical-Based Protocol for the Rational Design of Covalent Inhibitors

(2016) Tanja Schirmeister et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Dipeptidyl Nitroalkenes as Potent Reversible Inhibitors of Cysteine Proteases Rhodesain and Cruzain

(2016) Antonio Latorre et al.   ACS Medicinal Chemistry Letters

A Perspective on the Kinetics of Covalent and Irreversible Inhibition

(2016) John M. Strelow   SLAS Discovery

Rapid Determination of the Specificity Constant of Irreversible Inhibitors (kinact/KI) by Means of an Endpoint Competition Assay

(2015) Ikuo Miyahisa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The Design of Covalent Allosteric Drugs

(2015) Ruth Nussinov et al.   Annual Review of Pharmacology and Toxicology

First Quantum Mechanics/Molecular Mechanics Studies of the Inhibition Mechanism of Cruzain by Peptidyl Halomethyl Ketones

(2015) Kemel Arafet et al.   BIOCHEMISTRY

Covalent Docking Predicts Substrates for Haloalkanoate Dehalogenase Superfamily Phosphatases

(2015) Nir London et al.   BIOCHEMISTRY

ASBench: benchmarking sets for allosteric discovery: Fig. 1.

(2015) Wenkang Huang et al.   BIOINFORMATICS

Accurate Composite and Fragment-Based Quantum Chemical Models for Large Molecules

(2015) Krishnan Raghavachari et al.   CHEMICAL REVIEWS

Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies

(2015) Renato A. Bauer   DRUG DISCOVERY TODAY

Quantum Mechanics/Molecular Mechanics Modeling of Covalent Addition between EGFR–Cysteine 797 and N-(4-Anilinoquinazolin-6-yl) Acrylamide

(2015) Luigi Capoferri et al.   Journal of Chemical Information and Modeling

DOCKTITE—A Highly Versatile Step-by-Step Workflow for Covalent Docking and Virtual Screening in the Molecular Operating Environment

(2015) Christoph Scholz et al.   Journal of Chemical Information and Modeling

Analysis of Different Fragmentation Strategies on a Variety of Large Peptides: Implementation of a Low Level of Theory in Fragment-Based Methods Can Be a Crucial Factor

(2015) Arjun Saha et al.   Journal of Chemical Theory and Computation

ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB

(2015) James A. Maier et al.   Journal of Chemical Theory and Computation

Systematic Study of the Glutathione (GSH) Reactivity of N-Arylacrylamides: 1. Effects of Aryl Substitution

(2015) Victor J. Cee et al.   JOURNAL OF MEDICINAL CHEMISTRY

Accurate and Reliable Prediction of Relative Ligand Binding Potency in Prospective Drug Discovery by Way of a Modern Free-Energy Calculation Protocol and Force Field

(2015) Lingle Wang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Theory and Applications of Covalent Docking in Drug Discovery: Merits and Pitfalls

(2015) Hezekiel Kumalo et al.   MOLECULES

BindingDB in 2015: A public database for medicinal chemistry, computational chemistry and systems pharmacology

(2015) Michael K. Gilson et al.   NUCLEIC ACIDS RESEARCH

Covalent docking using autodock: Two-point attractor and flexible side chain methods

(2015) Giulia Bianco et al.   PROTEIN SCIENCE

Recent computational advances in the identification of allosteric sites in proteins

(2014) Shaoyong Lu et al.   DRUG DISCOVERY TODAY

Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase

(2014) Matthew S Davids et al.   Future Oncology

Structure-Based Virtual Screening Approach for Discovery of Covalently Bound Ligands

(2014) Dora Toledo Warshaviak et al.   Journal of Chemical Information and Modeling

Docking Covalent Inhibitors: A Parameter Free Approach To Pose Prediction and Scoring

(2014) Kai Zhu et al.   Journal of Chemical Information and Modeling

Chemical and Computational Methods for the Characterization of Covalent Reactive Groups for the Prospective Design of Irreversible Inhibitors

(2014) Mark E. Flanagan et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases

(2014) Stefan G. Kathman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rings in Drugs

(2014) Richard D. Taylor et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design of Reversible, Cysteine-Targeted Michael Acceptors Guided by Kinetic and Computational Analysis

(2014) Shyam Krishnan et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Covalent docking of large libraries for the discovery of chemical probes

(2014) Nir London et al.   Nature Chemical Biology

Current challenges in peptide-based drug discovery

(2014) Laszlo Otvos et al.   Frontiers in Chemistry

Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes

(2013) J. A. Dubovsky et al.   BLOOD

De Novo Design of Drug-Like Molecules by a Fragment-Based Molecular Evolutionary Approach

(2013) Kentaro Kawai et al.   Journal of Chemical Information and Modeling

Modeling Local Structural Rearrangements Using FEP/REST: Application to Relative Binding Affinity Predictions of CDK2 Inhibitors

(2013) Lingle Wang et al.   Journal of Chemical Theory and Computation

Dimers of Dimers (DOD): A New Fragment-Based Method Applied to Large Water Clusters

(2013) Arjun Saha et al.   Journal of Chemical Theory and Computation

Fundamental Reaction Pathway for Peptide Metabolism by Proteasome: Insights from First-Principles Quantum Mechanical/Molecular Mechanical Free Energy Calculations

(2013) Donghui Wei et al.   JOURNAL OF PHYSICAL CHEMISTRY B

Electrophilic Fragment-Based Design of Reversible Covalent Kinase Inhibitors

(2013) Rand M. Miller et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Covalent EGFR inhibitor analysis reveals importance of reversible interactions to potency and mechanisms of drug resistance

(2013) P. A. Schwartz et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Different Ways through Which Specificity Works in Orthosteric and Allosteric Drugs

(2012) Ruth Nussinov et al.   CURRENT PHARMACEUTICAL DESIGN

CovalentDock: Automated covalent docking with parameterized covalent linkage energy estimation and molecular geometry constraints

(2012) Xuchang Ouyang et al.   JOURNAL OF COMPUTATIONAL CHEMISTRY

Alchemical free energy methods for drug discovery: progress and challenges

(2011) John D Chodera et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity

(2011) Candice E Paulsen et al.   Nature Chemical Biology

The resurgence of covalent drugs

(2011) Juswinder Singh et al.   NATURE REVIEWS DRUG DISCOVERY

Strategies for discovering and derisking covalent, irreversible enzyme inhibitors

(2010) Douglas S Johnson et al.   Future Medicinal Chemistry

Rapid Context-Dependent Ligand Desolvation in Molecular Docking

(2010) Michael M. Mysinger et al.   Journal of Chemical Information and Modeling

Structural Fluctuations in Enzyme-Catalyzed Reactions: Determinants of Reactivity in Fatty Acid Amide Hydrolase from Multivariate Statistical Analysis of Quantum Mechanics/Molecular Mechanics Paths

(2010) Alessio Lodola et al.   Journal of Chemical Theory and Computation

The roles of drug metabolism in the pathogenesis of T-cell-mediated drug hypersensitivity

(2009) Sidonie Nelly Lavergne et al.   Current Opinion in Allergy and Clinical Immunology

AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility

(2009) Garrett M. Morris et al.   JOURNAL OF COMPUTATIONAL CHEMISTRY

Constrained Peptidomimetics Reveal Detailed Geometric Requirements of Covalent Prolyl Oligopeptidase Inhibitors

(2009) Janice Lawandi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Binding of Small-Molecule Ligands to Proteins: “What You See” Is Not Always “What You Get”

(2009) David L. Mobley et al.   STRUCTURE

Reversibility of Covalent Electrophile−Protein Adducts and Chemical Toxicity

(2008) De Lin et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Immune-Mediated Adverse Drug Reactions

(2008) Jack Uetrecht   CHEMICAL RESEARCH IN TOXICOLOGY

Perspective on Free-Energy Perturbation Calculations for Chemical Equilibria

(2008) William L. Jorgensen et al.   Journal of Chemical Theory and Computation

Idiosyncratic Drug Reactions: Past, Present, and Future

(2007) Jack Uetrecht   CHEMICAL RESEARCH IN TOXICOLOGY