arXiv subjects

Charlotte Rochereau

Publications and source records attributed to Charlotte Rochereau.

3 recordsLinked to original sources

arXiv2023

A billion years of evolution manifest in nanosecond protein dynamics

Protein dynamics form a critical bridge between protein structure and function, yet the impact of evolution on ultrafast processes inside proteins remains enigmatic. This study delves deep into nanosecond-scale protein dynamics of a structurally and functionally conserved protein across species separated by almost a billion years, investigating ten homologs in complex with their ligand. By inducing a photo-triggered destabilization of the ligand inside the binding pocket, we resolved distinct kinetic footprints for each homolog via transient infrared spectroscopy . Strikingly, we found a cascade of rearrangements within the protein complex which manifest in three discrete time points of dynamic activity, conserved over hundreds of millions of years within a narrow window. Among these processes, one displays a subtle temporal shift correlating with evolutionary divergence, suggesting reduced selective pressure in the past. Our study not only uncovers the impact of evolution on molecular processes in a specific case, but has also the potential to initiate a novel field of scientific inquiry within molecular paleontology, where species are compared and classified based on the rapid pace of protein dynamic processes; a field which connects the shortest conceivable time scale in living matter (10^-9 s) with the largest ones (10^16 s).

physics.bio-ph↗

arXiv2023

Ankh: Optimized Protein Language Model Unlocks General-Purpose Modelling

As opposed to scaling-up protein language models (PLMs), we seek improving performance via protein-specific optimization. Although the proportionality between the language model size and the richness of its learned representations is validated, we prioritize accessibility and pursue a path of data-efficient, cost-reduced, and knowledge-guided optimization. Through over twenty experiments ranging from masking, architecture, and pre-training data, we derive insights from protein-specific experimentation into building a model that interprets the language of life, optimally. We present Ankh, the first general-purpose PLM trained on Google's TPU-v4 surpassing the state-of-the-art performance with fewer parameters (<10% for pre-training, <7% for inference, and <30% for the embedding dimension). We provide a representative range of structure and function benchmarks where Ankh excels. We further provide a protein variant generation analysis on High-N and One-N input data scales where Ankh succeeds in learning protein evolutionary conservation-mutation trends and introducing functional diversity while retaining key structural-functional characteristics. We dedicate our work to promoting accessibility to research innovation via attainable resources.

cs.LG↗

arXiv2021

Neural language modeling of free word order argument structure

Neural language models trained with a predictive or masked objective have proven successful at capturing short and long distance syntactic dependencies. Here, we focus on verb argument structure in German, which has the interesting property that verb arguments may appear in a relatively free order in subordinate clauses. Therefore, checking that the verb argument structure is correct cannot be done in a strictly sequential fashion, but rather requires to keep track of the arguments' cases irrespective of their orders. We introduce a new probing methodology based on minimal variation sets and show that both Transformers and LSTM achieve a score substantially better than chance on this test. As humans, they also show graded judgments preferring canonical word orders and plausible case assignments. However, we also found unexpected discrepancies in the strength of these effects, the LSTMs having difficulties rejecting ungrammatical sentences containing frequent argument structure types (double nominatives), and the Transformers tending to overgeneralize, accepting some infrequent word orders or implausible sentences that humans barely accept.

cs.CL↗