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

Project Information

PREDACTED

Grant agreement ID: 101021207

DOI

10.3030/101021207

EC signature date 11 May 2021

Start date 1 October 2021

End date 30 September 2026

Funded under

EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 482 332,00

EU contribution

€ 2 482 332,00

2 482 332,00

Coordinated by

UNIVERSITY OF BRISTOL
United Kingdom

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Publications

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

Author(s): Matteo Castelli, Andrea Magni, Giorgio Bonollo, Silvia Pavoni, Francesco Frigerio, A. Sofia F. Oliveira, Fabrizio Cinquini, Stefano A. Serapian, Giorgio Colombo
Published in: Protein Science, Issue 33, 2024, Page(s) e4880, ISSN 0961-8368
Publisher: 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

Author(s): 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
Published in: Journal of the American Chemical Society, Issue 147, 2025, Page(s) 42583–42590, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.5c13620

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

Author(s): Bundit Kamsri, Pharit Kamsri, Auradee Punkvang, Aunlika Chimprasit, Patchreenart Saparpakorn, Supa Hannongbua, James Spencer, A. Sofia F. Oliveira, Adrian J. Mulholland, Pornpan Pungpo
Published in: Biochemistry, Issue 63, 2024, Page(s) 1493-1504, ISSN 0006-2960
Publisher: 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”

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

AI.zymes – A modular platform for evolutionary enzyme design

Author(s): Lucas Primus Merlicek, Jannik Neumann, Abbie Lear, Vivian Degiorgi, Moor de Waal, Tudor-Stefan Cotet, Adrian J. Mulholland, Hans Adrian Bunzel
Published in: Angewandte Chemie International Edition, Issue 64, 2026, Page(s) e202507031, ISSN 1433-7851
Publisher: 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

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

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

Author(s): A Sofia F Oliveira, Deborah K Shoemark, Andrew D Davidson, Imre Berger, Christiane Schaffitzel, Adrian J Mulholland
Published in: Journal of Molecular Cell Biology, Issue 15, 2023, Page(s) mjad021, ISSN 1759-4685
Publisher: 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

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

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

Author(s): Christopher Frölich, H. Adrian Bunzel, Karol Buda, Adrian J. Mulholland, Marc W. van der Kamp, Pål J. Johnsen, Hanna-Kirsti S. Leiros, Nobuhiko Tokuriki
Published in: Nature Catalysis, 2024, ISSN 2520-1158
Publisher: Spring Nature
DOI: 10.1038/s41929-024-01117-4

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

Author(s): 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'
Published in: The International Journal of High Computing Applications, Issue 37, 2023, Page(s) 28-44, ISSN 1094-3420
Publisher: SAGE Publications
DOI: 10.1177/10943420221128233

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

Author(s): J. Jasmin Güven, Marko Hanževački, Papu Kalita, Adrian J. Mulholland, Antonia S. J. S. Mey
Published in: The Journal of Physical Chemistry B, Issue 128, 2024, Page(s) 12416-12424, ISSN 1520-6106
Publisher: 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

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

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

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

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

Author(s): 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
Published in: eLife, Issue 13, 2026, Page(s) RP97313, ISSN 2050-084X
Publisher: 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

Author(s): 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
Published in: Journal of Open Source Software, Issue 10, 2025, Page(s) 8118, ISSN 2475-9066
Publisher: Open Journals
DOI: 10.21105/joss.08118

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

Author(s): Deeks, Helen M.; Zinovjev, Kirill; Barnoud, Jonathan; Mulholland, Adrian J.; van der Kamp, Marc W.; Glowacki, David R.
Published in: Scientific Reports, Issue 13, 2023, Page(s) 16665, ISSN 2045-2322
Publisher: 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 Mycobacterium tuberculosis and Hit Validation by Biological Assays

Author(s): 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
Published in: Journal of Chemical Information and Modeling, Issue 64, 2024, Page(s) 5991-6002, ISSN 1549-9596
Publisher: American Chemical Society
DOI: 10.1021/acs.jcim.4c00511

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

Author(s): 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
Published in: ACS Catalysis, Issue 14, 2024, Page(s) 4379-4394, ISSN 2155-5435
Publisher: American Chemical Society
DOI: 10.1021/acscatal.3c05584

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

Author(s): Michael Beer, Ana Sofia F. Oliveira, Catherine L. Tooke, Philip Hinchliffe, Angie Tsz Yan Li, Balazs Balega, James Spencer, Adrian J. Mulholland
Published in: Chemical Science, Issue 15, 2026, Page(s) 17232, ISSN 2041-6539
Publisher: 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

Author(s): 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
Published in: Angewandte Chemie International Edition, Issue 64, 2026, Page(s) e202515743, ISSN 1433-7851
Publisher: 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

Author(s): H. T. Henry Chan; A. Sofia F. Oliveira; Christopher J. Schofield; Adrian J. Mulholland; Fernanda Duarte
Published in: JACS Au, Issue 3, 2023, Page(s) 1767–1774, ISSN 2691-3704
Publisher: 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

Author(s): 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
Published in: Journal of Chemical Information and Modeling, Issue 65, 2025, Page(s) 8322-8334, ISSN 1549-9596
Publisher: 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)

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

Monooxygenase Activity of Indoleamine 2,3-Dioxygenase

Author(s): 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
Published in: Journal of the American Chemical Society, Issue 148, 2026, Page(s) 6178-6187, ISSN 0002-7863
Publisher: American Chemical Society
DOI: 10.1021/jacs.5c17552

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

Author(s): 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
Published in: RSC Medicinal Chemistry, Issue 16, 2025, Page(s) 5441-5455, ISSN 2632-8682
Publisher: 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

Author(s): Catherine L. Tooke; Philip Hinchliffe; Michael Beer; Kirill Zinovjev; Charlotte K. Colenso; Christopher J. Schofield; Adrian J. Mulholland; James Spencer
Published in: Journal of the American Chemical Society, Issue 145, 2023, Page(s) 7166-7180, ISSN 0002-7863
Publisher: 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

Author(s): 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
Published in: Antibody Therapeutics, Issue 6, 2023, Page(s) 277-297, ISSN 2516-4236
Publisher: Oxford University Press
DOI: 10.1093/abt/tbad024

Heme binding to the SARS-CoV-2 spike glycoprotein

Author(s): 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
Published in: Journal of Biological Chemistry, Issue 299, 2023, Page(s) 105014, ISSN 0021-9258
Publisher: 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

Author(s): 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
Published in: FEBS Letters, Issue 599, 2026, Page(s) 3284-3300, ISSN 0014-5793
Publisher: Elsevier BV
DOI: 10.1101/2025.03.13.642993

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

Author(s): 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
Published in: Proceedings of the National Academy of Sciences, Issue 120, 2023, Page(s) e2306046120, ISSN 1091-6490
Publisher: 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

Author(s): Balazs Balega, Michael Beer, James Spencer, Giorgio Colombo, Stefano A. Serapian, A. Sofia F. Oliveira, Adrian J. Mulholland
Published in: Molecular Physics, Issue 123, 2025, ISSN 0026-8976
Publisher: Taylor & Francis
DOI: 10.1080/00268976.2024.2428350

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

Author(s): Ewa I. Chudyk; Michael Beer; Michael A. L. Limb; Charlotte A. Jones; James Spencer; Marc W. van der Kamp; Adrian J. Mulholland
Published in: ACS Infectious Diseases, Issue 8, 2022, ISSN 2373-8227
Publisher: American Chemical Society
DOI: 10.1021/acsinfecdis.2c00152

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

Author(s): 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
Published in: Nature Communications, Issue 14, 2023, Page(s) 6260, ISSN 2041-1723
Publisher: 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

Author(s): 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
Published in: Biochimica et Biophysica Acta (BBA) - General Subjects, Issue 1869, 2025, Page(s) 130827, ISSN 0304-4165
Publisher: Elsevier BV
DOI: 10.1016/j.bbagen.2025.130827

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

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

Fluctuation relations to calculate protein redox potentials from molecular dynamics simulations

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

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