Predictive computational models for Enzyme Dynamics, Antimicrobial resistance, Catalysis and Thermoadaptation for Evolution and Design

Informations projet

PREDACTED

N° de convention de subvention: 101021207

DOI

10.3030/101021207

Date de signature de la CE 11 Mai 2021

Date de début 1 Octobre 2021

Date de fin 30 Septembre 2026

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 482 332,00

Contribution de l’UE

€ 2 482 332,00

Coordonné par

UNIVERSITY OF BRISTOL
United Kingdom

CORDIS fournit des liens vers les livrables publics et les publications des projets HORIZON.

Les liens vers les livrables et les publications des projets du 7e PC, ainsi que les liens vers certains types de résultats spécifiques tels que les jeux de données et les logiciels, sont récupérés dynamiquement sur OpenAIRE .

Publications

Peer reviewed articles (35)

Molecular mechanisms of chaperone‐directed protein folding: Insights from atomistic simulations

Auteurs: Matteo Castelli, Andrea Magni, Giorgio Bonollo, Silvia Pavoni, Francesco Frigerio, A. Sofia F. Oliveira, Fabrizio Cinquini, Stefano A. Serapian, Giorgio Colombo
Publié dans: Protein Science, Numéro 33, 2024, Page(s) e4880, ISSN 0961-8368
Éditeur: Cold Spring Harbor Laboratory Press
DOI: 10.1002/pro.4880

Metallo-coiled Coil Stabilization via Chemical Cross-Linking: Implications for Gd(III)-Based MRI Contrast Agents

Auteurs: Kate A. Hadley, Marco Ricci, Marko Hanzevacki, Helena Bernstein, Hiruni S. Jayasekera, Aneika C. Leney, Adrian J. Mulholland, Fabio Carniato, Mauro Botta, Melanie M. Britton, Anna F. A. Peacock
Publié dans: Journal of the American Chemical Society, Numéro 147, 2025, Page(s) 42583–42590, ISSN 0002-7863
Éditeur: American Chemical Society
DOI: 10.1021/jacs.5c13620

Signal Propagation in the ATPase Domain of <i>Mycobacterium tuberculosis</i> DNA Gyrase from Dynamical-Nonequilibrium Molecular Dynamics Simulations

Auteurs: Bundit Kamsri, Pharit Kamsri, Auradee Punkvang, Aunlika Chimprasit, Patchreenart Saparpakorn, Supa Hannongbua, James Spencer, A. Sofia F. Oliveira, Adrian J. Mulholland, Pornpan Pungpo
Publié dans: Biochemistry, Numéro 63, 2024, Page(s) 1493-1504, ISSN 0006-2960
Éditeur: American Chemical Society
DOI: 10.1021/acs.biochem.4c00161

Comment on: “Computer Simulations Reveal an Entirely Entropic Activation Barrier for the Chemical Step in a Designer Enzyme”

Auteurs: Abbie Lear; J. L. Ross Anderson; Donald Hilvert; Vickery L. Arcus; Marc W. van der Kamp; H. Adrian Bunzel; Adrian J. Mulholland
Publié dans: ACS Catalysis, Numéro 13, 2023, Page(s) 10527–10530, ISSN 2155-5435
Éditeur: American Chemical Society
DOI: 10.1021/acscatal.3c01906

AI.zymes – A modular platform for evolutionary enzyme design

Auteurs: Lucas Primus Merlicek, Jannik Neumann, Abbie Lear, Vivian Degiorgi, Moor de Waal, Tudor-Stefan Cotet, Adrian J. Mulholland, Hans Adrian Bunzel
Publié dans: Angewandte Chemie International Edition, Numéro 64, 2026, Page(s) e202507031, ISSN 1433-7851
Éditeur: John Wiley & Sons Ltd.
DOI: 10.1101/2025.01.18.633707

Electric Fields Are a Key Determinant of Carbapenemase Activity in Class A β-Lactamases

Auteurs: Hira Jabeen, Michael Beer, James Spencer, Marc W. van der Kamp, H. Adrian Bunzel, Adrian J. Mulholland
Publié dans: ACS Catalysis, Numéro 14, 2024, Page(s) 7166-7172, ISSN 2155-5435
Éditeur: American Chemical Society
DOI: 10.1021/acscatal.3c05302

SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid

Auteurs: A Sofia F Oliveira, Deborah K Shoemark, Andrew D Davidson, Imre Berger, Christiane Schaffitzel, Adrian J Mulholland
Publié dans: Journal of Molecular Cell Biology, Numéro 15, 2023, Page(s) mjad021, ISSN 1759-4685
Éditeur: Oxford University Press
DOI: 10.1093/jmcb/mjad021

Quantum Mechanics/Molecular Mechanics Simulations Distinguish Insulin-Regulated Aminopeptidase Substrate (Oxytocin) and Inhibitor (Angiotensin IV) and Reveal Determinants of Activity and Inhibition

Auteurs: Marko Hanževački, Rebecca M. Twidale, Eric J.M. Lang, Will Gerrard, David W. Wright, Vid Stojevic, Adrian J. Mulholland
Publié dans: Journal of Chemical Information and Modeling, Numéro 65, 2025, Page(s) 6261-6272, ISSN 1549-9596
Éditeur: American Chemical Society
DOI: 10.1021/acs.jcim.5c00869

Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase

Auteurs: Christopher Frölich, H. Adrian Bunzel, Karol Buda, Adrian J. Mulholland, Marc W. van der Kamp, Pål J. Johnsen, Hanna-Kirsti S. Leiros, Nobuhiko Tokuriki
Publié dans: Nature Catalysis, 2024, ISSN 2520-1158
Éditeur: Spring Nature
DOI: 10.1038/s41929-024-01117-4

"#COVIDisAirborne: AI-enabled multiscale computational microscopy of delta SARS-CoV-2 in a respiratory aerosol"

Auteurs: Abigail Dommer, Lorenzo Casalino, Fiona Kearns, Mia Rosenfeld, Nicholas Wauer, Surl-Hee Ahn, John Russo, Sofia Oliveira, Clare Morris, Anthony Bogetti, Anda Trifan, Alexander Brace, Terra Sztain, Austin Clyde, Heng Ma, Chakra Chennubhotla, Hyungro Lee, Matteo Turilli, Syma Khalid, Teresa Tamayo-Mendoza, Matthew Welborn, Anders Christensen, Daniel GA Smith, Zhuoran Qiao, Sai K Sirumalla, Michael O'
Publié dans: The International Journal of High Computing Applications, Numéro 37, 2023, Page(s) 28-44, ISSN 1094-3420
Éditeur: SAGE Publications
DOI: 10.1177/10943420221128233

Protocols for Metallo- and Serine-β-Lactamase Free Energy Predictions: Insights from Cross-Class Inhibitors

Auteurs: J. Jasmin Güven, Marko Hanževački, Papu Kalita, Adrian J. Mulholland, Antonia S. J. S. Mey
Publié dans: The Journal of Physical Chemistry B, Numéro 128, 2024, Page(s) 12416-12424, ISSN 1520-6106
Éditeur: American Chemical Society
DOI: 10.1021/acs.jpcb.4c06379

A Reflection on the Use of Molecular Simulation to Respond to SARS-CoV-2 Pandemic Threats

Auteurs: Lorenzo Casalino, Carlos A. Ramos-Guzmán, Rommie E. Amaro, Carlos Simmerling, Alessio Lodola, Adrian J. Mulholland, Katarzyna Świderek, Vicent Moliner
Publié dans: The Journal of Physical Chemistry Letters, Numéro 16, 2025, Page(s) 3249-3263, ISSN 1948-7185
Éditeur: American Chemical Society
DOI: 10.1021/acs.jpclett.4c03654

Decrypting Allostery in Membrane-Bound K-Ras4B Using Complementary <i>In Silico</i> Approaches Based on Unbiased Molecular Dynamics Simulations

Auteurs: Matteo Castelli; Filippo Marchetti; Sílvia Osuna; A. Sofia F. Oliveira; Adrian J. Mulholland; Stefano A. Serapian; Giorgio Colombo
Publié dans: Journal of the American Chemical Society, Numéro 146, 2024, Page(s) 901-919, ISSN 0002-7863
Éditeur: American Chemical Society
DOI: 10.1021/jacs.3c11396

Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike

Auteurs: A Sofia F Oliveira, Fiona L Kearns, Mia A Rosenfeld, Lorenzo F Casalino, Lorenzo Tulli, Imre Berger, Christiane Schaffitzel, Andrew D Davidson, Rommie E Amaro, Adrian J Mulholland
Publié dans: eLife, Numéro 13, 2026, Page(s) RP97313, ISSN 2050-084X
Éditeur: eLife Sciences Publications
DOI: 10.1101/2023.11.06.565757

NanoVer Server: A Python Package for Serving Real-Time Multi-User Interactive Molecular Dynamics in Virtual Reality

Auteurs: Harry J. Stroud, Mark D. Wonnacott, Jonathan Barnoud, Rhoslyn Roebuck Williams, Mohamed Dhouioui, Adam McSloy, Ludovica Aisa, Luis E. Toledo, Phil Bates, Adrian J. Mulholland, David R. Glowacki
Publié dans: Journal of Open Source Software, Numéro 10, 2025, Page(s) 8118, ISSN 2475-9066
Éditeur: Open Journals
DOI: 10.21105/joss.08118

Free energy along drug-protein binding pathways interactively sampled in virtual reality

Auteurs: Deeks, Helen M.; Zinovjev, Kirill; Barnoud, Jonathan; Mulholland, Adrian J.; van der Kamp, Marc W.; Glowacki, David R.
Publié dans: Scientific Reports, Numéro 13, 2023, Page(s) 16665, ISSN 2045-2322
Éditeur: Nature Publishing Group
DOI: 10.1038/s41598-023-43523-x

Ligand-Based Virtual Screening for Discovery of Indole Derivatives as Potent DNA Gyrase ATPase Inhibitors Active against <i>Mycobacterium tuberculosis</i> and Hit Validation by Biological Assays

Auteurs: Bongkochawan Pakamwong, Paptawan Thongdee, Bundit Kamsri, Naruedon Phusi, Somjintana Taveepanich, Kampanart Chayajarus, Pharit Kamsri, Auradee Punkvang, Supa Hannongbua, Jidapa Sangswan, Khomson Suttisintong, Sanya Sureram, Prasat Kittakoop, Poonpilas Hongmanee, Pitak Santanirand, Jiraporn Leanpolchareanchai, James Spencer, Adrian J. Mulholland, Pornpan Pungpo
Publié dans: Journal of Chemical Information and Modeling, Numéro 64, 2024, Page(s) 5991-6002, ISSN 1549-9596
Éditeur: American Chemical Society
DOI: 10.1021/acs.jcim.4c00511

Cooperative Conformational Transitions Underpin the Activation Heat Capacity in the Temperature Dependence of Enzyme Catalysis

Auteurs: Emma J. Walker; Carlin J. Hamill; Rory Crean; Michael S. Connolly; Annmaree K. Warrender; Kirsty L. Kraakman; Erica J. Prentice; Alistair Steyn-Ross; Moira Steyn-Ross; Christopher R. Pudney; Marc W. van der Kamp; Louis A. Schipper; Adrian J. Mulholland; Vickery L. Arcus
Publié dans: ACS Catalysis, Numéro 14, 2024, Page(s) 4379-4394, ISSN 2155-5435
Éditeur: American Chemical Society
DOI: 10.1021/acscatal.3c05584

Dynamical Responses Predict a Distal Site that Modulates Activity in an Antibiotic Resistance Enzyme

Auteurs: Michael Beer, Ana Sofia F. Oliveira, Catherine L. Tooke, Philip Hinchliffe, Angie Tsz Yan Li, Balazs Balega, James Spencer, Adrian J. Mulholland
Publié dans: Chemical Science, Numéro 15, 2026, Page(s) 17232, ISSN 2041-6539
Éditeur: Royal Society of Chemistry
DOI: 10.1101/2024.04.29.591639

Solvent Channels and Electric Fields Guide Proton Delivery to the Active Site of Heme Peroxidases

Auteurs: Reynier Suardíaz, Shakir Ali Siddiqui, Hanna Kwon, Marc W. van der Kamp, Lola González‐Sánchez, Peter C. E. Moody, Emma L. Raven, Adrian J. Mulholland
Publié dans: Angewandte Chemie International Edition, Numéro 64, 2026, Page(s) e202515743, ISSN 1433-7851
Éditeur: John Wiley & Sons Ltd.
DOI: 10.1002/anie.202515743

Dynamical Nonequilibrium Molecular Dynamics Simulations Identify Allosteric Sites and Positions Associated with Drug Resistance in the SARS-CoV-2 Main Protease

Auteurs: H. T. Henry Chan; A. Sofia F. Oliveira; Christopher J. Schofield; Adrian J. Mulholland; Fernanda Duarte
Publié dans: JACS Au, Numéro 3, 2023, Page(s) 1767–1774, ISSN 2691-3704
Éditeur: American Chemical Society
DOI: 10.1021/jacsau.3c00185

Dynamic Behavior and Substrate Interactions of the Polymyxin Resistance Determinant MCR-1 Investigated by Molecular Dynamics Simulations in the Membrane Environment

Auteurs: Emily Lythell, Jack Badley, Reynier Suardíaz, Catherine R. Gurr, Catherine L. Tooke, Philip Hinchliffe, A. Sofia F. Oliveira, Marc W. Van der Kamp, James Spencer, Adrian J. Mulholland
Publié dans: Journal of Chemical Information and Modeling, Numéro 65, 2025, Page(s) 8322-8334, ISSN 1549-9596
Éditeur: American Chemical Society
DOI: 10.1021/acs.jcim.5c01338

All Roads Lead to Carbinolamine: QM/MM Study of Enzymatic C–N Bond Cleavage in Anaerobic Glycyl Radical Enzyme Choline Trimethylamine-Lyase (CutC)

Auteurs: Marko Hanzevacki, J. Jasmin Güven, Philip Hinchliffe, John Shaw, Antonia S. J. S. Mey, Natalie Fey, James Spencer, Adrian J. Mulholland
Publié dans: The Journal of Physical Chemistry B, Numéro 129, 2025, Page(s) 9322-9332, ISSN 1520-6106
Éditeur: American Chemical Society
DOI: 10.1021/acs.jpcb.5c04023

Monooxygenase Activity of Indoleamine 2,3-Dioxygenase

Auteurs: Ali B. Lubis, Anna J. Bailey, Marko Hanževački, Christopher Williams, Mehul Jesani, Lola González-Sánchez, Christopher J. Arthur, Hannah C. Wilson, Andrea E. Gallio, Peter C. E. Moody, Matthew P. Crump, Adrian J. Mulholland, Allen M. Orville, Jonathan Clayden, Emma L. Raven
Publié dans: Journal of the American Chemical Society, Numéro 148, 2026, Page(s) 6178-6187, ISSN 0002-7863
Éditeur: American Chemical Society
DOI: 10.1021/jacs.5c17552

Electrostatic interactions influence diazabicyclooctane inhibitor potency against OXA-48-like β-lactamases

Auteurs: Joseph F. Hoff, Kirsty E. Goudar, Karina Calvopiña, Michael Beer, Philip Hinchliffe, John M. Shaw, Catherine L. Tooke, Yuiko Takebayashi, Andrew F. Cadzow, Nicholas J. Harmer, Adrian J. Mulholland, Christopher J. Schofield, James Spencer
Publié dans: RSC Medicinal Chemistry, Numéro 16, 2025, Page(s) 5441-5455, ISSN 2632-8682
Éditeur: Royal Society of Chemistry (RSC)
DOI: 10.1039/d5md00512d

Tautomer-Specific Deacylation and Ω-Loop Flexibility Explain the Carbapenem-Hydrolyzing Broad-Spectrum Activity of the KPC-2 β-Lactamase

Auteurs: Catherine L. Tooke; Philip Hinchliffe; Michael Beer; Kirill Zinovjev; Charlotte K. Colenso; Christopher J. Schofield; Adrian J. Mulholland; James Spencer
Publié dans: Journal of the American Chemical Society, Numéro 145, 2023, Page(s) 7166-7180, ISSN 0002-7863
Éditeur: American Chemical Society
DOI: 10.1021/jacs.2c12123

In vitro generated antibodies guide thermostable ADDomer nanoparticle design for nasal vaccination and passive immunization against SARS-CoV-2

Auteurs: Dora Buzas, H Adrian Bunzel, Oskar Staufer, Emily J Milodowski, Grace L Edmunds, Joshua C Bufton, Beatriz V Vidana Mateo, Sathish K N Yadav, Kapil Gupta, Charlotte Fletcher, Maia Kavanagh Williamson, Alexandra Harrison, Ufuk Borucu, Julien Capin, Ore Francis, Georgia Balchin, Sophie Hall, Mirella Vivoli Vega, Fabien Durbesson, Renaud Vincentelli, Joe Roe, Linda Wooldridge, Rachel Burt, J L Ross An
Publié dans: Antibody Therapeutics, Numéro 6, 2023, Page(s) 277-297, ISSN 2516-4236
Éditeur: Oxford University Press
DOI: 10.1093/abt/tbad024

Heme binding to the SARS-CoV-2 spike glycoprotein

Auteurs: Samuel L Freeman, A Sofia F Oliveira, Andrea E Gallio, Annachiara Rosa, Maria K Simitakou, Christopher J Arthur, Adrian J Mulholland, Peter Cherepanov, Emma L Raven
Publié dans: Journal of Biological Chemistry, Numéro 299, 2023, Page(s) 105014, ISSN 0021-9258
Éditeur: American Society for Biochemistry and Molecular Biology Inc.
DOI: 10.1016/j.jbc.2023.105014

Mechanistic Basis for Inhibition of the Extended Spectrum Class A β-Lactamase GES-1 by Tazobactam and Enmetazobactam

Auteurs: Michael Beer, Philip Hinchliffe, Marko Hanževački, Christopher R. Bethel, Catherine L. Tooke, Marc W. van der Kamp, Krisztina M. Papp-Wallace, Robert A. Bonomo, Stuart Shapiro, Adrian J. Mulholland, James Spencer
Publié dans: FEBS Letters, Numéro 599, 2026, Page(s) 3284-3300, ISSN 0014-5793
Éditeur: Elsevier BV
DOI: 10.1101/2025.03.13.642993

An expandable, modular de novo protein platform for precision redox engineering

Auteurs: George H Hutchins, Claire EM Noble, H Adrian Bunzel, Christopher Williams, Paulina Dubiel, Sathish KN Yadav, Paul M Molinaro, Rob Barringer, Hector Blackburn, Benjamin J Hardy, Alice E Parnell, Charles Landau, Paul R Race, Thomas AA Oliver, Ronald L Koder, Matthew P Crump, Christiane Schaffitzel, A Sofia F Oliveira, Adrian J Mulholland, JL Ross Anderson
Publié dans: Proceedings of the National Academy of Sciences, Numéro 120, 2023, Page(s) e2306046120, ISSN 1091-6490
Éditeur: National Academy of Sciences
DOI: 10.1073/pnas.2306046120

Dynamical nonequilibrium molecular dynamics simulations reveal allosteric networks, signal transduction mechanisms, and sites associated with drug resistance in biomolecular systems

Auteurs: Balazs Balega, Michael Beer, James Spencer, Giorgio Colombo, Stefano A. Serapian, A. Sofia F. Oliveira, Adrian J. Mulholland
Publié dans: Molecular Physics, Numéro 123, 2025, ISSN 0026-8976
Éditeur: Taylor & Francis
DOI: 10.1080/00268976.2024.2428350

QM/MM Simulations Reveal the Determinants of Carbapenemase Activity in Class A β-Lactamases

Auteurs: Ewa I. Chudyk; Michael Beer; Michael A. L. Limb; Charlotte A. Jones; James Spencer; Marc W. van der Kamp; Adrian J. Mulholland
Publié dans: ACS Infectious Diseases, Numéro 8, 2022, ISSN 2373-8227
Éditeur: American Chemical Society
DOI: 10.1021/acsinfecdis.2c00152

Human cellular model systems of β-thalassemia enable in-depth analysis of disease phenotype

Auteurs: Deborah E Daniels; Ivan Ferrer-Vicens; J Hawksworth; Tatyana N Andrienko; Elizabeth M Finnie; Daniel C J Ferguson; A. Sofia F. Oliveira; Jenn-Yeu A. Szeto; Marieangela C Wilson; Jan Frayne
Publié dans: Nature Communications, Numéro 14, 2023, Page(s) 6260, ISSN 2041-1723
Éditeur: Nature Publishing Group
DOI: 10.1101/2022.09.01.506225

Hybrid virtual screening identifies dipyrazole carboxamide derivatives as novel direct InhA inhibitors with antitubercular activity

Auteurs: Auradee Punkvang, Bongkochawan Pakamwong, Naruedon Phusi, Paptawan Thongdee, Kampanart Chayajarus, Jidapa Sangswan, Kanjana Pangjit, Khomson Suttisintong, Jiraporn Leanpolchareanchai, Poonpilas Hongmanee, Pitak Santanirand, James Spencer, Adrian J. Mulholland, Sanya Sureram, Prasat Kittakoop, Pornpan Pungpo
Publié dans: Biochimica et Biophysica Acta (BBA) - General Subjects, Numéro 1869, 2025, Page(s) 130827, ISSN 0304-4165
Éditeur: Elsevier BV
DOI: 10.1016/j.bbagen.2025.130827

Hydrogen-bonding changes cause differences in imipenem breakdown activity in OXA-48 variants

Auteurs: Daojiong Wang, Adrian J. Mulholland, James Spencer, Marc W. van der Kamp
Publié dans: Journal of Chemical Information and Modeling, Numéro 66, 2026, Page(s) 5416–5428, ISSN 1549-9596
Éditeur: American Chemical Society
DOI: 10.64898/2026.01.20.700306

Non-peer reviewed articles (1)

Fluctuation relations to calculate protein redox potentials from molecular dynamics simulations

Auteurs: Oliveira, A. S. F.; Rubio, J.; Noble, C. E. M.; Anderson, J. L. R.; Anders, J.; Mulholland, A. J.
Publié dans: J. Chem. Theor. Comput., Numéro 20, 2023, Page(s) 385-395, ISSN 1549-9618
Éditeur: American Chemical Society
DOI: 10.1021/acs.jctc.3c00785