ANR-PRC MAPPLE (2023-2026)
MAssively Parallelized Polarizable Linear-scaling QM/MM for Enzymatic catalysis
Participants: Nicolas Ferré, Miquel Huix-Rotllant
Elucidating the mechanisms of enzymatic reactions is fundamental for designing more efficient biomimetic catalysts or protein mutants with enhanced catalytic activity. Accurate modeling of a multi-step catalytic cycle imposes three essential requirements: (i) a high-level quantum description of the reactive center, (ii) the correct sampling of the protein conformational space, and (iii) the simulation of processes occurring beyond the nanosecond time scale. The MAPPLE project aims at developing, implementing, validating, and applying a new QM/MD method for accurate description of enzymatic catalysis, by combining recent developments like linear-scaling quantum-chemical methods, fully variational QM-MM electrostatics employing polarizable atomistic forcefield, and software optimization for High-Performance Computing. This new QM/MD method will be applied to a microalgal alkane synthase photocatalysis, which uses light to transform fatty acids into higher alkanes.
ANR-PRC ULTRArchae (2022-2025)
Ultrafast structural dynamics
of Archaerhodopsin–3 in its fluorescent state
Participants: Nicolas Ferré, Miquel Huix-Rotllant, Vincent Ledentu, Gustavo Cardenas, Dario Barreiro-Lage
Archaerhodopsin-3 (AR-3), a photo-activated proton pump from Halorubrum sodomense, is the progenitor of an entire class of genetically encoded fluorescent membrane voltage indicators (GEVI). Like in other microbial rhodopsins, absorption of visible light triggers in AR-3 the retinal chromophore reversible photoisomerization which leads to the existence of several intermediates with lifetimes covering the sub-picosecond to millisecond time scale. At variance with other 1-photon-based fluorescent rhodopsins, wild-type AR-3 fluorescence is taking place after 3-photon absorption. The underlying molecular mechanism is still unknown, motivating the present investigation.
Using advanced methods of ultrafast electronic and vibrational spectroscopy and state-of-the-art quantum chemistry methods, combined with time-resolved X-ray crystallography, the ULTRArchae consortium will provide for the first time a detailed mechanistic understanding of the structure-function relationship leading to unusual fluorescence properties in AR-3 and its variants.
ANR-PRCi FEMTO-SWITCH (2024-2026)
A Combined Theoretical and
Experimental Study of Ultrafast Biomimetic
Photoswitches – Towards Rational Design Rules
Partner: Miquel Huix-Rotllant
The main objective of FEMTO-Switch is to establish rational grounds as to how the chemical structure of ultrafast photo-switches controls the molecular energetics and excited state dynamics of ultrafast photo-switches at the conical intersections (CInts). To this end, we will employ femtosecond UV/VIS/NIR and photoelectron spectroscopy (fs-PES) in the liquid phase, coupled to quantum chemistry calculations, performed at M. Huix-Rotllant group. When used with femtosecond XUV pulses, fs-PES is a powerful method, that can follow ionization energies of transient electronic states on ultrafast timescales, virtually for all regions of exited and ground states along the reaction pathway. Since the CInts are the branching points for forward vs. backward reaction, i.e., controlling the quantum yield, FEMTO-Switch aims at studying these critical points. The modern implementation in the liquid phase will be applied to two types of bio-mimetic molecular switches with the focus on revealing the impact of chemical substitutions on the energy landscape along the reaction path leading to and around the CInts. (Image taken from https://doi.org/10.1038/s41467-022-33695-x)
ERC AdG SubNano (2019-2024)
Computational Photochemistry in the Long Timescale
Principal investigator: Mario Barbatti
The goal of SubNano is to massively speed up dynamics simulations of photoexcited molecules to address sub-nanosecond phenomena (that is, one thousand times above the current simulation limits).
Such methods will allow exploring phenomena, like vibrational relaxation, fluorescence, slow internal conversion, intersystem crossing, which have been left aside by computational chemistry, too focused on ultrafast processes.
The sub-ns methodology will be employed to investigate the long timescale nonadiabatic dynamics of photoinduced processes in nucleic acids, including DNA photostabilization via excitonic processes, biological fluorescent markers, and DNA pyrimidine-dimer repair.
FetOpen BoostCrop (2019-2022)
Boosting Crop Growth using Natural Product and Synthesis Enabled Solar Harvesting
Work package manager: Mario Barbatti
BoostCrop is an EU funded research project that has a long term vision to develop a highly efficient, environmentally friendly, and affordable foliar spray for crop growth enhancement and thus sustainable food security. See our plan for further details.
Our team combines the expertise of 6 participant universities with 13 university-based lead investigators, one government institute with one section leader, one SME with two group leaders and encompasses the 3 major disciplines of Chemistry, Physics, Biology.
ANR- shapeNread (2019-2023)
Conformational design for high throughput MS/MS reading of digital polymers
Participants: Anouk Siri / Didier Siri
The shapeNread project aims at optimizing the tridimensional structure of encoded synthetic polymers to allow their high throughput sequencing by coupling tandem mass spectrometry with ion mobility spectrometry. Synthesis of these polymers will allow binary information to be contained in blocks, each labeled with a specific tag to enable their distinction in terms of mass and conformation. To do so, tags will be conceived by molecular modeling based on their propensity to provide different collision cross sections for all blocks. Once released in a first activation stage, block-containing fragments could hence be separated by ion mobility and further be individually sequenced after a second activation stage. Such a structural design would allow high throughput reading of molecularly encoded information (at least one decabyte per chain) by MS/MS-IMS-MS/MS. Appropriate development of the MS-DECODER software will enable automated data analysis.
