ANR-PRC MAPPLE (2023-2026)

MAssively Parallelized Polarizable Linear-scaling QM/MM for Enzymatic catalysis

Partners: 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

Partners: Nicolas Ferré, Miquel Huix-Rotllant, Vincent Ledentu, Gustavo Cardenas

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.


Multiple trajectories towards excited states

Partner: Miquel Huix-Rotllant

Multicross aims at understanding transition metal photophysics to a new level of detail thanks to a joint experimental and theoretical research program spanning three laboratories and two countries. Ultrafast optical spectroscopy and X-ray techniques will be pushed to time resolutions approaching 10 fs.

Quantum models will be used to solve time-dependent Schrodinger equation to follow the photoinduced wavepacket motion and dispersion along different excited state trajectories that will be controlled by different pump laser pulses. Because the same physical model will be able to explain the different experimental findings, the outcomes will be little biased and the resulting representations can be used to clarify the mechanisms behind the unexpected properties of ultrafast intersystem crossing of transition metal compounds.

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

Partners: 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.