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

Informazioni relative al progetto

PREDACTED

ID dell’accordo di sovvenzione: 101021207

DOI

10.3030/101021207

Data della firma CE 11 Maggio 2021

Data di avvio 1 Ottobre 2021

Data di completamento 30 Settembre 2026

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 2 482 332,00

Contributo UE

€ 2 482 332,00

Coordinato da

UNIVERSITY OF BRISTOL
United Kingdom

CORDIS fornisce collegamenti ai risultati finali pubblici e alle pubblicazioni dei progetti ORIZZONTE.

I link ai risultati e alle pubblicazioni dei progetti del 7° PQ, così come i link ad alcuni tipi di risultati specifici come dataset e software, sono recuperati dinamicamente da .OpenAIRE .

Pubblicazioni

Peer reviewed articles (35)

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

Autori: Matteo Castelli, Andrea Magni, Giorgio Bonollo, Silvia Pavoni, Francesco Frigerio, A. Sofia F. Oliveira, Fabrizio Cinquini, Stefano A. Serapian, Giorgio Colombo
Pubblicato in: Protein Science, Numero 33, 2024, Pagina/e e4880, ISSN 0961-8368
Editore: 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

Autori: 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
Pubblicato in: Journal of the American Chemical Society, Numero 147, 2025, Pagina/e 42583–42590, ISSN 0002-7863
Editore: 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

Autori: Bundit Kamsri, Pharit Kamsri, Auradee Punkvang, Aunlika Chimprasit, Patchreenart Saparpakorn, Supa Hannongbua, James Spencer, A. Sofia F. Oliveira, Adrian J. Mulholland, Pornpan Pungpo
Pubblicato in: Biochemistry, Numero 63, 2024, Pagina/e 1493-1504, ISSN 0006-2960
Editore: 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”

Autori: Abbie Lear; J. L. Ross Anderson; Donald Hilvert; Vickery L. Arcus; Marc W. van der Kamp; H. Adrian Bunzel; Adrian J. Mulholland
Pubblicato in: ACS Catalysis, Numero 13, 2023, Pagina/e 10527–10530, ISSN 2155-5435
Editore: American Chemical Society
DOI: 10.1021/acscatal.3c01906

AI.zymes – A modular platform for evolutionary enzyme design

Autori: Lucas Primus Merlicek, Jannik Neumann, Abbie Lear, Vivian Degiorgi, Moor de Waal, Tudor-Stefan Cotet, Adrian J. Mulholland, Hans Adrian Bunzel
Pubblicato in: Angewandte Chemie International Edition, Numero 64, 2026, Pagina/e e202507031, ISSN 1433-7851
Editore: 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

Autori: Hira Jabeen, Michael Beer, James Spencer, Marc W. van der Kamp, H. Adrian Bunzel, Adrian J. Mulholland
Pubblicato in: ACS Catalysis, Numero 14, 2024, Pagina/e 7166-7172, ISSN 2155-5435
Editore: American Chemical Society
DOI: 10.1021/acscatal.3c05302

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

Autori: A Sofia F Oliveira, Deborah K Shoemark, Andrew D Davidson, Imre Berger, Christiane Schaffitzel, Adrian J Mulholland
Pubblicato in: Journal of Molecular Cell Biology, Numero 15, 2023, Pagina/e mjad021, ISSN 1759-4685
Editore: 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

Autori: Marko Hanževački, Rebecca M. Twidale, Eric J.M. Lang, Will Gerrard, David W. Wright, Vid Stojevic, Adrian J. Mulholland
Pubblicato in: Journal of Chemical Information and Modeling, Numero 65, 2025, Pagina/e 6261-6272, ISSN 1549-9596
Editore: American Chemical Society
DOI: 10.1021/acs.jcim.5c00869

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

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

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

Autori: 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'
Pubblicato in: The International Journal of High Computing Applications, Numero 37, 2023, Pagina/e 28-44, ISSN 1094-3420
Editore: SAGE Publications
DOI: 10.1177/10943420221128233

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

Autori: J. Jasmin Güven, Marko Hanževački, Papu Kalita, Adrian J. Mulholland, Antonia S. J. S. Mey
Pubblicato in: The Journal of Physical Chemistry B, Numero 128, 2024, Pagina/e 12416-12424, ISSN 1520-6106
Editore: 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

Autori: Lorenzo Casalino, Carlos A. Ramos-Guzmán, Rommie E. Amaro, Carlos Simmerling, Alessio Lodola, Adrian J. Mulholland, Katarzyna Świderek, Vicent Moliner
Pubblicato in: The Journal of Physical Chemistry Letters, Numero 16, 2025, Pagina/e 3249-3263, ISSN 1948-7185
Editore: 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

Autori: Matteo Castelli; Filippo Marchetti; Sílvia Osuna; A. Sofia F. Oliveira; Adrian J. Mulholland; Stefano A. Serapian; Giorgio Colombo
Pubblicato in: Journal of the American Chemical Society, Numero 146, 2024, Pagina/e 901-919, ISSN 0002-7863
Editore: American Chemical Society
DOI: 10.1021/jacs.3c11396

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

Autori: 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
Pubblicato in: eLife, Numero 13, 2026, Pagina/e RP97313, ISSN 2050-084X
Editore: 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

Autori: 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
Pubblicato in: Journal of Open Source Software, Numero 10, 2025, Pagina/e 8118, ISSN 2475-9066
Editore: Open Journals
DOI: 10.21105/joss.08118

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

Autori: Deeks, Helen M.; Zinovjev, Kirill; Barnoud, Jonathan; Mulholland, Adrian J.; van der Kamp, Marc W.; Glowacki, David R.
Pubblicato in: Scientific Reports, Numero 13, 2023, Pagina/e 16665, ISSN 2045-2322
Editore: 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

Autori: 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
Pubblicato in: Journal of Chemical Information and Modeling, Numero 64, 2024, Pagina/e 5991-6002, ISSN 1549-9596
Editore: American Chemical Society
DOI: 10.1021/acs.jcim.4c00511

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

Autori: 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
Pubblicato in: ACS Catalysis, Numero 14, 2024, Pagina/e 4379-4394, ISSN 2155-5435
Editore: American Chemical Society
DOI: 10.1021/acscatal.3c05584

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

Autori: Michael Beer, Ana Sofia F. Oliveira, Catherine L. Tooke, Philip Hinchliffe, Angie Tsz Yan Li, Balazs Balega, James Spencer, Adrian J. Mulholland
Pubblicato in: Chemical Science, Numero 15, 2026, Pagina/e 17232, ISSN 2041-6539
Editore: 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

Autori: 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
Pubblicato in: Angewandte Chemie International Edition, Numero 64, 2026, Pagina/e e202515743, ISSN 1433-7851
Editore: 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

Autori: H. T. Henry Chan; A. Sofia F. Oliveira; Christopher J. Schofield; Adrian J. Mulholland; Fernanda Duarte
Pubblicato in: JACS Au, Numero 3, 2023, Pagina/e 1767–1774, ISSN 2691-3704
Editore: 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

Autori: 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
Pubblicato in: Journal of Chemical Information and Modeling, Numero 65, 2025, Pagina/e 8322-8334, ISSN 1549-9596
Editore: 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)

Autori: Marko Hanzevacki, J. Jasmin Güven, Philip Hinchliffe, John Shaw, Antonia S. J. S. Mey, Natalie Fey, James Spencer, Adrian J. Mulholland
Pubblicato in: The Journal of Physical Chemistry B, Numero 129, 2025, Pagina/e 9322-9332, ISSN 1520-6106
Editore: American Chemical Society
DOI: 10.1021/acs.jpcb.5c04023

Monooxygenase Activity of Indoleamine 2,3-Dioxygenase

Autori: 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
Pubblicato in: Journal of the American Chemical Society, Numero 148, 2026, Pagina/e 6178-6187, ISSN 0002-7863
Editore: American Chemical Society
DOI: 10.1021/jacs.5c17552

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

Autori: 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
Pubblicato in: RSC Medicinal Chemistry, Numero 16, 2025, Pagina/e 5441-5455, ISSN 2632-8682
Editore: 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

Autori: Catherine L. Tooke; Philip Hinchliffe; Michael Beer; Kirill Zinovjev; Charlotte K. Colenso; Christopher J. Schofield; Adrian J. Mulholland; James Spencer
Pubblicato in: Journal of the American Chemical Society, Numero 145, 2023, Pagina/e 7166-7180, ISSN 0002-7863
Editore: 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

Autori: 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
Pubblicato in: Antibody Therapeutics, Numero 6, 2023, Pagina/e 277-297, ISSN 2516-4236
Editore: Oxford University Press
DOI: 10.1093/abt/tbad024

Heme binding to the SARS-CoV-2 spike glycoprotein

Autori: 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
Pubblicato in: Journal of Biological Chemistry, Numero 299, 2023, Pagina/e 105014, ISSN 0021-9258
Editore: 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

Autori: 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
Pubblicato in: FEBS Letters, Numero 599, 2026, Pagina/e 3284-3300, ISSN 0014-5793
Editore: Elsevier BV
DOI: 10.1101/2025.03.13.642993

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

Autori: 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
Pubblicato in: Proceedings of the National Academy of Sciences, Numero 120, 2023, Pagina/e e2306046120, ISSN 1091-6490
Editore: 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

Autori: Balazs Balega, Michael Beer, James Spencer, Giorgio Colombo, Stefano A. Serapian, A. Sofia F. Oliveira, Adrian J. Mulholland
Pubblicato in: Molecular Physics, Numero 123, 2025, ISSN 0026-8976
Editore: Taylor & Francis
DOI: 10.1080/00268976.2024.2428350

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

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

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

Autori: 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
Pubblicato in: Nature Communications, Numero 14, 2023, Pagina/e 6260, ISSN 2041-1723
Editore: 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

Autori: 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
Pubblicato in: Biochimica et Biophysica Acta (BBA) - General Subjects, Numero 1869, 2025, Pagina/e 130827, ISSN 0304-4165
Editore: Elsevier BV
DOI: 10.1016/j.bbagen.2025.130827

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

Autori: Daojiong Wang, Adrian J. Mulholland, James Spencer, Marc W. van der Kamp
Pubblicato in: Journal of Chemical Information and Modeling, Numero 66, 2026, Pagina/e 5416–5428, ISSN 1549-9596
Editore: 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

Autori: Oliveira, A. S. F.; Rubio, J.; Noble, C. E. M.; Anderson, J. L. R.; Anders, J.; Mulholland, A. J.
Pubblicato in: J. Chem. Theor. Comput., Numero 20, 2023, Pagina/e 385-395, ISSN 1549-9618
Editore: American Chemical Society
DOI: 10.1021/acs.jctc.3c00785