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

Información del proyecto

PREDACTED

Identificador del acuerdo de subvención: 101021207

DOI

10.3030/101021207

Fecha de la firma de la CE 11 Mayo 2021

Fecha de inicio 1 Octubre 2021

Fecha de finalización 30 Septiembre 2026

Financiado con arreglo a

• EXCELLENT SCIENCE - European Research Council (ERC)

Coste total

€ 2 482 332,00

Aportación de la UE

€ 2 482 332,00

Coordinado por

UNIVERSITY OF BRISTOL
United Kingdom

CORDIS proporciona enlaces a los documentos públicos y las publicaciones de los proyectos de los programas marco HORIZONTE.

Los enlaces a los documentos y las publicaciones de los proyectos del Séptimo Programa Marco, así como los enlaces a algunos tipos de resultados específicos, como conjuntos de datos y «software», se obtienen dinámicamente de OpenAIRE .

Publicaciones

Peer reviewed articles (35)

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

Autores: Matteo Castelli, Andrea Magni, Giorgio Bonollo, Silvia Pavoni, Francesco Frigerio, A. Sofia F. Oliveira, Fabrizio Cinquini, Stefano A. Serapian, Giorgio Colombo
Publicado en: Protein Science, Edición 33, 2024, Página(s) e4880, ISSN 0961-8368
Editor: 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

Autores: 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
Publicado en: Journal of the American Chemical Society, Edición 147, 2025, Página(s) 42583–42590, ISSN 0002-7863
Editor: 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

Autores: Bundit Kamsri, Pharit Kamsri, Auradee Punkvang, Aunlika Chimprasit, Patchreenart Saparpakorn, Supa Hannongbua, James Spencer, A. Sofia F. Oliveira, Adrian J. Mulholland, Pornpan Pungpo
Publicado en: Biochemistry, Edición 63, 2024, Página(s) 1493-1504, ISSN 0006-2960
Editor: 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”

Autores: Abbie Lear; J. L. Ross Anderson; Donald Hilvert; Vickery L. Arcus; Marc W. van der Kamp; H. Adrian Bunzel; Adrian J. Mulholland
Publicado en: ACS Catalysis, Edición 13, 2023, Página(s) 10527–10530, ISSN 2155-5435
Editor: American Chemical Society
DOI: 10.1021/acscatal.3c01906

AI.zymes – A modular platform for evolutionary enzyme design

Autores: Lucas Primus Merlicek, Jannik Neumann, Abbie Lear, Vivian Degiorgi, Moor de Waal, Tudor-Stefan Cotet, Adrian J. Mulholland, Hans Adrian Bunzel
Publicado en: Angewandte Chemie International Edition, Edición 64, 2026, Página(s) e202507031, ISSN 1433-7851
Editor: 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

Autores: Hira Jabeen, Michael Beer, James Spencer, Marc W. van der Kamp, H. Adrian Bunzel, Adrian J. Mulholland
Publicado en: ACS Catalysis, Edición 14, 2024, Página(s) 7166-7172, ISSN 2155-5435
Editor: American Chemical Society
DOI: 10.1021/acscatal.3c05302

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

Autores: A Sofia F Oliveira, Deborah K Shoemark, Andrew D Davidson, Imre Berger, Christiane Schaffitzel, Adrian J Mulholland
Publicado en: Journal of Molecular Cell Biology, Edición 15, 2023, Página(s) mjad021, ISSN 1759-4685
Editor: 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

Autores: Marko Hanževački, Rebecca M. Twidale, Eric J.M. Lang, Will Gerrard, David W. Wright, Vid Stojevic, Adrian J. Mulholland
Publicado en: Journal of Chemical Information and Modeling, Edición 65, 2025, Página(s) 6261-6272, ISSN 1549-9596
Editor: American Chemical Society
DOI: 10.1021/acs.jcim.5c00869

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

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

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

Autores: 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'
Publicado en: The International Journal of High Computing Applications, Edición 37, 2023, Página(s) 28-44, ISSN 1094-3420
Editor: SAGE Publications
DOI: 10.1177/10943420221128233

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

Autores: J. Jasmin Güven, Marko Hanževački, Papu Kalita, Adrian J. Mulholland, Antonia S. J. S. Mey
Publicado en: The Journal of Physical Chemistry B, Edición 128, 2024, Página(s) 12416-12424, ISSN 1520-6106
Editor: 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

Autores: Lorenzo Casalino, Carlos A. Ramos-Guzmán, Rommie E. Amaro, Carlos Simmerling, Alessio Lodola, Adrian J. Mulholland, Katarzyna Świderek, Vicent Moliner
Publicado en: The Journal of Physical Chemistry Letters, Edición 16, 2025, Página(s) 3249-3263, ISSN 1948-7185
Editor: 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

Autores: Matteo Castelli; Filippo Marchetti; Sílvia Osuna; A. Sofia F. Oliveira; Adrian J. Mulholland; Stefano A. Serapian; Giorgio Colombo
Publicado en: Journal of the American Chemical Society, Edición 146, 2024, Página(s) 901-919, ISSN 0002-7863
Editor: American Chemical Society
DOI: 10.1021/jacs.3c11396

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

Autores: 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
Publicado en: eLife, Edición 13, 2026, Página(s) RP97313, ISSN 2050-084X
Editor: 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

Autores: 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
Publicado en: Journal of Open Source Software, Edición 10, 2025, Página(s) 8118, ISSN 2475-9066
Editor: Open Journals
DOI: 10.21105/joss.08118

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

Autores: Deeks, Helen M.; Zinovjev, Kirill; Barnoud, Jonathan; Mulholland, Adrian J.; van der Kamp, Marc W.; Glowacki, David R.
Publicado en: Scientific Reports, Edición 13, 2023, Página(s) 16665, ISSN 2045-2322
Editor: 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

Autores: 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
Publicado en: Journal of Chemical Information and Modeling, Edición 64, 2024, Página(s) 5991-6002, ISSN 1549-9596
Editor: American Chemical Society
DOI: 10.1021/acs.jcim.4c00511

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

Autores: 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
Publicado en: ACS Catalysis, Edición 14, 2024, Página(s) 4379-4394, ISSN 2155-5435
Editor: American Chemical Society
DOI: 10.1021/acscatal.3c05584

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

Autores: Michael Beer, Ana Sofia F. Oliveira, Catherine L. Tooke, Philip Hinchliffe, Angie Tsz Yan Li, Balazs Balega, James Spencer, Adrian J. Mulholland
Publicado en: Chemical Science, Edición 15, 2026, Página(s) 17232, ISSN 2041-6539
Editor: 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

Autores: 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
Publicado en: Angewandte Chemie International Edition, Edición 64, 2026, Página(s) e202515743, ISSN 1433-7851
Editor: 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

Autores: H. T. Henry Chan; A. Sofia F. Oliveira; Christopher J. Schofield; Adrian J. Mulholland; Fernanda Duarte
Publicado en: JACS Au, Edición 3, 2023, Página(s) 1767–1774, ISSN 2691-3704
Editor: 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

Autores: 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
Publicado en: Journal of Chemical Information and Modeling, Edición 65, 2025, Página(s) 8322-8334, ISSN 1549-9596
Editor: 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)

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

Monooxygenase Activity of Indoleamine 2,3-Dioxygenase

Autores: 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
Publicado en: Journal of the American Chemical Society, Edición 148, 2026, Página(s) 6178-6187, ISSN 0002-7863
Editor: American Chemical Society
DOI: 10.1021/jacs.5c17552

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

Autores: 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
Publicado en: RSC Medicinal Chemistry, Edición 16, 2025, Página(s) 5441-5455, ISSN 2632-8682
Editor: 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

Autores: Catherine L. Tooke; Philip Hinchliffe; Michael Beer; Kirill Zinovjev; Charlotte K. Colenso; Christopher J. Schofield; Adrian J. Mulholland; James Spencer
Publicado en: Journal of the American Chemical Society, Edición 145, 2023, Página(s) 7166-7180, ISSN 0002-7863
Editor: 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

Autores: 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
Publicado en: Antibody Therapeutics, Edición 6, 2023, Página(s) 277-297, ISSN 2516-4236
Editor: Oxford University Press
DOI: 10.1093/abt/tbad024

Heme binding to the SARS-CoV-2 spike glycoprotein

Autores: 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
Publicado en: Journal of Biological Chemistry, Edición 299, 2023, Página(s) 105014, ISSN 0021-9258
Editor: 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

Autores: 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
Publicado en: FEBS Letters, Edición 599, 2026, Página(s) 3284-3300, ISSN 0014-5793
Editor: Elsevier BV
DOI: 10.1101/2025.03.13.642993

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

Autores: 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
Publicado en: Proceedings of the National Academy of Sciences, Edición 120, 2023, Página(s) e2306046120, ISSN 1091-6490
Editor: 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

Autores: Balazs Balega, Michael Beer, James Spencer, Giorgio Colombo, Stefano A. Serapian, A. Sofia F. Oliveira, Adrian J. Mulholland
Publicado en: Molecular Physics, Edición 123, 2025, ISSN 0026-8976
Editor: Taylor & Francis
DOI: 10.1080/00268976.2024.2428350

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

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

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

Autores: 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
Publicado en: Nature Communications, Edición 14, 2023, Página(s) 6260, ISSN 2041-1723
Editor: 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

Autores: 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
Publicado en: Biochimica et Biophysica Acta (BBA) - General Subjects, Edición 1869, 2025, Página(s) 130827, ISSN 0304-4165
Editor: Elsevier BV
DOI: 10.1016/j.bbagen.2025.130827

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

Autores: Daojiong Wang, Adrian J. Mulholland, James Spencer, Marc W. van der Kamp
Publicado en: Journal of Chemical Information and Modeling, Edición 66, 2026, Página(s) 5416–5428, ISSN 1549-9596
Editor: 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

Autores: Oliveira, A. S. F.; Rubio, J.; Noble, C. E. M.; Anderson, J. L. R.; Anders, J.; Mulholland, A. J.
Publicado en: J. Chem. Theor. Comput., Edición 20, 2023, Página(s) 385-395, ISSN 1549-9618
Editor: American Chemical Society
DOI: 10.1021/acs.jctc.3c00785