Contacts:
Supervisor(s):
Prof. Benedetta Mennucci and Prof. Lorenzo Cupellini
Title of the PhD project:
Bridging Quantum Mechanics and Machine Learning for Simulating Complex Systems Interacting with Light
Abstract of the PhD project:
Light plays a pivotal role in various chemical and biochemical processes. These processes typically occur in condensed phases, where the surrounding environment significantly influences the reactions.
Molecular dynamics (MD) is a powerful tool to study complex systems. In particular, composite techniques in which MD is coupled to quantum mechanics/molecular mechanics (QM/MM) models are essential to describe light-induced phenomena in such systems. However, these accurate techniques cannot be used to obtain statistically relevant data on realistic systems, due to their high computational cost. The aim of the project is to develop new multiscale techniques of limited computational cost while keeping a high accuracy of the description and to apply them to the investigation of complex systems interacting with light, from photochemistry to spectroscopy.
Publications:
• M. Nottoli, D. Castrignano, P. Mazzeo, L. Cupellini, B. Stamm, (2026), Making excited state MD faster: extrapolation of transition densities for TD-DFT calculations, ChemRxiv preprint https://doi.org/10.26434/chemrxiv-2026-mqwxc
• P. Mazzeo, L. Cupellini, B. Mennucci, Multiscale Machine Learning Prediction of Infrared Spectra of Solvated Molecules, (2026), J. Chem. Theory Comput., https://doi.org/10.1021/acs.jctc.5c01959
• M. Cascone*, P. Mazzeo*, L. Cupellini, B. Mennucci, Multiscale Simulation of Photoinduced Electron Transfer in Cryptochrome 4 from European Robin and Pigeon Indicates a Conserved Dynamics, (2025), J. Phys. Chem. Lett., 16, 34, 8877-8884 https://doi.org/10.1021/acs.jpclett.5c01814 *Co-first author.
• L. Zhang, P. Mazzeo, M. Nottoli, E. Cignoni, L. Cupellini, B. Stamm, A symmetry-preserving and transferable representation for learning the Kohn-Sham density matrix, (2025), arXiv preprint https://doi.org/10.48550/arXiv.2503.08400
• G. Londi, G. Salvadori, P. Mazzeo, L. Cupellini and B. Mennucci, Protein-driven electron transfer process in a fatty acid photodecarboxylase, (2024), J. Am. Chem. Soc., 5, 1, 158-168 https://doi.org/10.1021/jacsau.4c00853
• P. Mazzeo, E. Cignoni, A. Arcidiacono, L. Cupellini and B. Mennucci, Electrostatic Embedding Machine Learning for Ground and Excited State Molecular Dynamics of Solvated Molecules, (2024), Digit. Discov., 3, 12, 2560-2571 https://doi.org/10.1039/D4DD00295D
• A. Arcidiacono, E. Cignoni, P. Mazzeo, L. Cupellini and B. Mennucci, Predicting Solvatochromism of Chromophores in Proteins through QM/MM and Machine Learning, (2024) J. Phys. Chem. A, 128, 18, 3646-3658, https://doi.org/10.1021/acs.jpca.4c00249
• G. Salvadori, P. Mazzeo, D. Accomasso, L. Cupellini and B. Mennucci, Deciphering photoreceptors through atomistic modeling from light absorption to conformational response, (2023), J. Mol. Biol., 168358, https://doi.org/10.1016/j.jmb.2023.168358
• F. Pes, É. Polack, P. Mazzeo, G. Dusson, B. Stamm and F. Lipparini, A Quasi Time-Reversible Scheme Based on Density Matrix Extrapolation on the Grassmann Manifold for Born–Oppenheimer Molecular Dynamics, (2023), J. Phys. Chem. Lett., 14, 43, 9720–9726, https://doi.org/10.1021/acs.jpclett.3c02098
• M. Nottoli, M. Bondanza, P. Mazzeo, L. Cupellini, C. Curutchet, D. Loco, L. Lagardère, J. P. Piquemal, B. Mennucci and F. Lipparini, QM/AMOEBA description of properties and dynamics of embedded molecules, (2023), Wiley Interdiscip. Rev. Comput. Mol. Sci. 13, e1674, https://doi.org/10.1002/wcms.1674
• P. Mazzeo, S. Hashem, F. Lipparini, L. Cupellini and B. Mennucci, Fast Method for Excited-State Dynamics in Complex Systems and Its Application to the Photoactivation of a Blue Light Using Flavin Photoreceptor, (2023), J. Phys. Chem. Lett., 14, 5, 1222–1229, https://doi.org/10.1021/acs.jpclett.2c03797
• M. Nottoli, P. Mazzeo, F. Lipparini, L. Cupellini and B. Mennucci, A ΔSCF model for excited states within a polarisable embedding, (2022), Mol. Phys., https://doi.org/10.1080/00268976.2022.2089605
Oral communications at conferences
• P. Mazzeo, E. Cignoni, A. Arcidiacono, S. Suarez Dou, A. Tkatchenko, L. Cupellini, B. Mennucci, Electrostatic embedding machine learning for ground and excited state molecular dynamics of complex systems, Chemistry for the Future 2025, Dipartimento di Chimica e Chimica Industiale, University of Pisa, 7-9 July 2025.
• P. Mazzeo, E. Cignoni, A. Arcidiacono, L. Cupellini, B. Mennucci, Excited-state dynamics of solvated molecules with multiscale machine learning, 3rd SIMPLAIX Workshop on Machine Learning for Multiscale Molecular Modeling, Studio Villa Bosch Heidelberg (Germany), 7-9 May 2025.
• P. Mazzeo, S. Hashem, F. Lipparini, L. Cupellini and B. Mennucci, Excited-state SCF Dynamics in Complex Systems: Unraveling the Photoactivation of a Blue-Light Using Flavin Photoreceptor, Tinker Developers Workshop 2024: New Trends in Modeling, Le Benedettine University of Pisa’s conference center, Pisa (Italy), 29-31 May 2024.
• P. Mazzeo, S. Hashem, M. Nottoli, F. Lipparini, L. Cupellini and B. Mennucci, A Fast Method for Polarizable QM/MM Excited-State Dynamics in Complex Systems, DCTC 2023-VIII Congresso Nazionale della Divisione di Chimica Teorica e Computazionale della SCI, Scuola Normale Superiore, Pisa (Italy), 20-22 September 2023.
• P. Mazzeo, S. Hashem, F. Lipparini, L. Cupellini and B. Mennucci, Unraveling the Photoactivation of a Blue-Light Using Flavin Photoreceptor through Excited-State SCF Dynamics, Chemistry for the Future 2023, Dipartimento di Chimica e Chimica Industriale, Università di Pisa (Italy), 28-30 June 2023.
Poster communications at conferences:
• P. Mazzeo, E. Cignoni, A. Arcidiacono, L. Cupellini, B. Mennucci, Excited-state dynamics of solvated molecules with multiscale machine learning, WATOC 2025, Oslo Kongressenter, Oslo (Norway), 22-27 June 2025.
• P. Mazzeo, E. Cignoni, A. Arcidiacono, L. Cupellini and B. Mennucci, Exploring Intramolecular Proton Transfer Dynamics with Machine Learning Multiscale Simulations, Chemistry for the future 2024, Dipartimento di Chimica e Chimica Industriale, Università di Pisa (Italy), 3-5 July 2024.
• P. Mazzeo, S. Hashem, Michele Nottoli, F. Lipparini, L. Cupellini and B. Mennucci, A Fast Method for Polarizable QM/MM Excited-State Dynamics in Complex Systems, 1st ViRAPID Workshop 2024, University of Vienna, Austria, 26-29 February 2024.
• P. Mazzeo, S. Hashem, F. Lipparini, L. Cupellini and B. Mennucci, Unraveling the Photoactivation of a Blue-Light Using Flavin Photoreceptor through Excited-State SCF Dynamics, Chemistry for the Future 2023, Dipartimento di Chimica e Chimica Industriale, Università di Pisa (Italy), 28-30 June 2023.
• P. Mazzeo, S. Hashem, F. Lipparini, L. Cupellini and B. Mennucci, Unraveling the Photoactivation of a Blue-Light Using Flavin Photoreceptor through Excited-State SCF Dynamics, EuChemS CompChem 2023, Thessaloniki (Greece), 27-31 August 2023.
