arXiv subjects

Yves-Henri Sanejouand

Publications and source records attributed to Yves-Henri Sanejouand.

At least 19 recordsLinked to original sources

arXiv2025

Using protein blocks to build custom fragment libraries from protein structures

The remarkable structural diversity of modern proteins reflects millions of years of evolution, during which sequence space has expanded while many structural features remain conserved. This conservation is evident not only among homologous proteins but also in the recurrence of supersecondary motifs across unrelated proteins, underscoring the abundance and robustness of these structural units. Here, we present a novel pipeline for generating customized protein fragment libraries using protein blocks (PBs) - a structural alphabet that encodes local backbone conformations. Our method efficiently extracts structurally similar fragments from a curated, non-redundant protein structure database by converting three-dimensional structures into one-dimensional PB sequences. By integrating predicted PB sequences with the PB-ALIGN and PB-kPRED tools, our approach identifies relevant fragments independently of sequence homology. Fragment quality is further assessed using a new scoring function that combines secondary structure similarity and PB alignment metrics. The resulting libraries contain fragments of at least seven PBs (11 amino acid residues), covering over 70% of the local backbone structure. Our results demonstrate that PBs enable efficient mining of high-quality structural fragments from diverse protein spaces, including proteins with disordered regions. The pipeline is accessible as an online tool (PB-Frag, https://pbpred-us2b.univ-nantes.fr/pbfrag ).

q-bio.QM↗

arXiv2024

A pair of possible supernovae Refsdal in the Pantheon+ sample

On December 1980, supernova 1980N was discovered in NGC 1316, a galaxy of the Fornax cluster. Three months later, supernova 1981D was observed in the same galaxy. The light curves of these two supernovae Ia were found to be virtually identical, suggesting that they are images of the same event, the delay between them being due to strong gravitational lensing. If so, as anticipated by Sjur Refsdal, the distance to the lens can be determined accurately, namely, 90 $\pm$ 1 kpc, meaning that it belongs to the outer halo of the Milky Way. Interestingly, there is another pair of possible images in the Pantheon+ sample, namely, supernovae 2013aa and 2017cbv, the distance to the lens being 702 $\pm$ 1 kpc, that is, nearly the same as the distance to the Andromeda galaxy. In both cases, given the relatively large angle of deviation of the supernova light by the lens, namely, 271" and 325", respectively, the lens has to be a compact object, with a mass to radius ratio over 150 M$_\odot$ R$_\odot^{-1}$. It is likely to be an ultra massive white dwarf.

astro-ph.GA↗

arXiv2024

A robust assessment of the local anisotropy of the Hubble constant

Magnitude predictions of $Λ$CDM, as parametrized by the Planck collaboration, are not consistent with the supernova data of the whole Pantheon+ sample even when, in order to take into account the uncertainty about its value, the Hubble constant is adjusted. This is a likely consequence of the increase of the number of low-redshift supernovae in the Pantheon+ sample, with respect to previous such samples. Indeed, when supernovae at redshifts below 0.035 are ignored, with H0=73.4 km/s/Mpc, $Λ$CDM predictions become consistent with Pantheon+ data. Interestingly, this is also the case when subsets of low-redshift supernovae roughly centered on the direction of the CMB dipole are considered, together with high-redshift ones, at least when CMB and peculiar velocities corrections are taken into account for the redshifts. These results seem robust, since they are also obtained with a simple, single-parameter tired-light model.

astro-ph.CO↗

arXiv2024

A framework for the next generation of stationary cosmological models

According to a new tired-light cosmological model, where H(z) = H 0 (1 + z), the number density of galaxies has been nearly constant over the last 10 Gyr, at least, meaning that, as far as galaxy counts are concerned, the Universe has been stationary. In this context, an analysis of the luminosity distances of quasars and supernovae Ia shows that the Universe is far from being as transparent as assumed nowadays, the photon lifetime along the line-of-sight being one third of the Hubble time. Such a low value could mean that there are huge amounts of grey dust in the inter galactic medium, that have so far escaped detection. It could also be a signature of new physics, namely, a consequence of the decay of photons into lighter particles. The tired-light model advocated in the present study would be falsified if, for instance, the time-dilation of remote events were shown to have a general character, that is, if it were definitely observed for phenomenons other than the light curves of supernovae Ia. On the other hand, further developments are needed in order to turn this model into an actual cosmology. In particular, the physical origin of the current stability of the Universe on galactic scales remains to be identified.

astro-ph.CO↗

arXiv2022

On the unknown proteins of eukaryotic proteomes

In order to study unknown proteins on a large scale, a reference system has been set up for the three major eukaryotic lineages, built with 36 proteomes as taxonomically diverse as possible. Proteins from 362 eukaryotic proteomes with no known homologue in this set were then analyzed, focusing noteworthy on singletons, that is, on unknown proteins with no known homologue in their own proteome. Consistently, according to Uniprot, for a given species, no more than 12% of the singletons thus found are known at the protein level. Also, since they rely on the information found in the alignment of homologous sequences, predictions of AlphaFold2 for their tridimensional structure are usually poor. In the case of metazoan species, the number of singletons seems to increase as a function of the evolutionary distance from the reference system. Interestingly, no such trend is found in the cases of viridiplantae and fungi, as if the timescale on which singletons are added to proteomes were different in metazoa and in other eukaryotic kingdoms. In order to confirm this phenomenon, further studies of proteomes closer to those of the reference system are however needed.

q-bio.GN↗

arXiv2022

At least three xenon binding sites in the glycine binding domain of the N-methyl D-aspartate receptor

Xenon can produce general anesthesia. Its main protein target is the N-methyl-D-aspartate receptor, a ionotropic channel playing a pivotal role in the function of the central nervous system. The molecular mechanisms allowing this noble gas to have such a specific effect remain obscure, probably as a consequence of the lack of structural data at the atomic level of detail. Herein, as a result of five independent molecular dynamics simulations, three different binding sites were found for xenon in the glycine binding domain of the N-methyl-D-aspartate receptor. The absolute binding free energy of xenon in these sites ranges between -8 and -14 kJ/mole. However, it depends significantly upon the protein conformer chosen for performing the calculation, suggesting that larger values could probably be obtained, if other conformers were considered. These three sites are next to each other, one of them being next to the glycine site. This could explain why the F758W and F758Y mutations can prevent competitive inhibition by xenon without affecting glycine binding.

q-bio.BM↗

arXiv2021

Normal-mode driven exploration of protein domain motions

Domain motions involved in the function of proteins can often be well described as a combination of motions along a handfull of low-frequency modes, that is, with the values of a few normal coordinates. This means that, when the functional motion of a protein is unknown, it should prove possible to predict it, since it amounts to guess a few values. However, without the help of additional experimental data, using normal coordinates for generating accurate conformers far away from the initial one is not so straightforward. To do so, a new approach is proposed: instead of building conformers directly with the values of a subset of normal coordinates, they are built in two steps, the conformer built with normal coordinates being just used for defining a set of distance constraints, the final conformer being built so as to match them. Note that this approach amounts to transform the problem of generating accurate protein conformers using normal coordinates into a better known one: the distance-geometry problem, which is herein solved with the help of the ROSETTA software. In the present study, this approach allowed to rebuild accurately six large amplitude conformational changes, using at most six low-frequency normal coordinates. As a consequence of the low-dimensionality of the corresponding subspace, random exploration also proved enough for generating low-energy conformers close to the known end-point of the conformational change of the LAO binding protein, lysozyme T4 and adenylate kinase.

q-bio.BM↗

arXiv2020

On the vibrational free energy of hydrated proteins

When the hydration shell of a protein is filled with at least 0.6 gram of water per gram of protein, a significant anti-correlation between the vibrational free energy and the potential energy of energy-minimized conformers is observed. This means that low potential energy, well-hydrated, protein conformers tend to be more rigid than high-energy ones. On the other hand, in the case of CASP target 624, when its hydration shell is filled, a significant average energy gap is observed between the crystal structure and the best conformers proposed during the prediction experiment, strongly suggesting that including explicit water molecules may help identifying unlikely conformers among good-looking ones.

q-bio.BM↗

arXiv2018

Has the density of sources of gamma-ray burts been constant over the last ten billion years ?

A generic tired-light mechanism is examined in which a photon, like any particle moving in a medium, experiences friction, that is, a force resisting its motion. If the velocity of light is assumed to be constant, this hypothesis yields a Hubble-like law which is also a consequence of the Rh = ct cosmology. Herein, it is used for estimating matter density as a function of redshift, allowing to show that the density of sources of long gamma-ray bursts appears to be nearly constant, up to z $\approx$ 4. Assuming that the later is a fair probe of the former, this means that matter density has been roughly constant over the last ten billion years, implying that, at least over this period, matter has been in an overall state of equilibrium.

physics.gen-ph↗

arXiv2017

Mutational dynamics of influenza A viruses: a principal component analysis of hemagglutinin sequences of subtype H1

A principal component analysis of a multiple sequence alignement of hemagglutinin sequences of subtype H1 has been performed, the sequences being encoded using the amino-acid property that maximizes the weight of the major component. In the case of this alignment, it happens to be a well-known hydrophobicity scale. Interestingly, sequences coming from human have large positive amplitudes along the major component before 2009, and large negative ones afterwards. This means that the 2009 pandemic was associated to a major change in the hydrophobicity pattern of hemagglutinin. The present analysis also highlights the high variability of viral sequences coming from swine. At a more general level, the method proposed in this paper allows to describe a sequence coming from an alignment with a set of numbers, the original point being that the choice of the corresponding property is driven by the data. This approach should allow the application of numerous methods to the study of large multiple sequence alignments.

q-bio.BM↗

arXiv2016

A singular mutation in the hemagglutinin of the 1918 pandemic virus

The influenza pandemic of 1918-1919 killed at least 50 million people. The reasons why this pandemic was so deadly remain largely unknown. However, It has been shown that the 1918 viral hemagglutinin allows to reproduce the hallmarks of the illness observed during the original pandemic. Thanks to the wealth of hemagglutinin sequences accumulated over the last decades, amino-acid substitutions that are found in the 1918-1919 sequences but rare otherwise can be identified with high confidence. Such an analysis reveals that Gly188, which is located within a key motif of the receptor binding site, is so rarely found in hemagglutinin sequences that, taken alone, it is likely to be deleterious. Monitoring this singular mutation in viral sequences may help prevent another dramatic pandemic.

q-bio.BM↗

arXiv2015

A simple Hubble-like law in lieu of dark energy

Within the frame of the $Λ$ cold dark matter paradigm, a dark energy component of unknown origin is expected to represent nearly 70% of the energy of the Universe. Herein, a non-standard form of the Hubble law is advocated, with the aim of providing safe grounds on which alternative cosmologies could be developed. Noteworthy, it yields an age-redshift relationship which is consistent with available data. Together with a straightforward analysis of gamma-ray burst counts, it further suggests that the observable Universe has been euclidean and static over the last 12 Gyr. Although a non-standard distance-duality relation is then required for interpreting luminosity distances, the magnitude-redshift relationship obtained is compatible with type Ia supernovae data.

astro-ph.CO↗

arXiv2013

Simplified flexibility analysis of proteins

A simple way to get insights about the possible functional motions of a protein is to perform a normal mode analysis (NMA). Indeed, it has been shown that low-frequency modes thus obtained are often closely related to domain motions involved in protein function. Moreover, because protein low-frequency modes are known to be robust, NMA can be performed using coarse-grained models. As a consequence, it can be done for large ensembles of conformations as well as for large systems, like the ribosome, whole virus capsids, etc. Unexpectedly, on the high-frequency side, modes obtained with cutoff-based coarse-grained models also seem able to provide useful insights on protein dynamical properties.

q-bio.BM↗

arXiv2011

Elastic Network Models: Theoretical and Empirical Foundations

Fifteen years ago Monique Tirion showed that the low-frequency normal modes of a protein are not significantly altered when non-bonded interactions are replaced by Hookean springs, for all atom pairs whose distance is smaller than a given cutoff value. Since then, it has been shown that coarse-grained versions of Tirion's model are able to provide fair insights on many dynamical properties of biological macromolecules. In this text, theoretical tools required for studying these so-called Elastic Network Models are described, focusing on practical issues and, in particular, on possible artifacts. Then, an overview of some typical results that have been obtained by studying such models is given.

q-bio.BM↗

arXiv2009

Empirical evidences in favor of a varying-speed-of-light

The empirical evidences in favor of the hypothesis that the speed of light decreases by a few centimeters per second each year are examined. Lunar laser ranging data are found to be consistent with this hypothesis, which also provides a straightforward explanation for the so-called Pioneer anomaly, that is, a time-dependent blue-shift observed when analyzing radio tracking data from distant spacecrafts, as well as an alternative explanation for both the apparent time-dilation of remote events and the apparent acceleration of the Universe. The main argument against this hypothesis, namely, the constancy of fine-structure and Rydberg constants, is discussed. Both of them being combinations of several physical constants, their constancy imply that, if the speed of light is indeed time-dependent, then at least two other "fundamental constants" have to vary as well. This defines strong constraints which will have to be fulfilled by future varying-speed-of-light theories.

physics.gen-ph↗

arXiv2009

Long-range energy transfer in proteins

Proteins are large and complex molecular machines. In order to perform their function, most of them need energy, e.g. either in the form of a photon, like in the case of the visual pigment rhodopsin, or through the breaking of a chemical bond, as in the presence of adenosine triphosphate (ATP). Such energy, in turn, has to be transmitted to specific locations, often several tens of Angstroms away from where it is initially released. Here we show, within the framework of a coarse-grained nonlinear network model, that energy in a protein can jump from site to site with high yields, covering in many instances remarkably large distances. Following single-site excitations, few specific sites are targeted, systematically within the stiffest regions. Such energy transfers mark the spontaneous formation of a localized mode of nonlinear origin at the destination site, which acts as an efficient energy-accumulating centre. Interestingly, yields are found to be optimum for excitation energies in the range of biologically relevant ones.

q-bio.BM↗

arXiv2009

Energy transfer in nonlinear network models of proteins

We investigate how nonlinearity and topological disorder affect the energy relaxation of local kicks in coarse-grained network models of proteins. We find that nonlinearity promotes long-range, coherent transfer of substantial energy to specific, functional sites, while depressing transfer to generic locations. Remarkably, transfer can be mediated by the self-localization of discrete breathers at distant locations from the kick, acting as efficient energy-accumulating centers.

cond-mat.soft↗

arXiv2008

Discrete breathers in protein structures

Recently, using a numerical surface cooling approach, we have shown that highly energetic discrete breathers (DB) can form in the stiffest parts of nonlinear network models of large protein structures. In the present study, using an analytical approach, we extend our previous results to low-energy discrete breathers as well as to smaller proteins We confirm and further scrutinize the striking site selectiveness of energy localisation in the presence of spatial disorder. In particular, we find that, as a sheer consequence of disorder, a non-zero energy gap for exciting a DB at a given site either exists or not. Remarkably, in the former case, the gaps arise as result of the impossibility of exciting small-amplitude modes in the first place. On the contrary, in the latter case, a small subset of linear edge modes act as accumulation points, whereby DBs can be continued to arbitrary small energies, while unavoidably approaching one of such normal modes. In particular, the case of the edge mode seems peculiar, its dispersion relation being simple and little system-dependent. Concerning the structure-dynamics relationship, we find that the regions of protein structures where DBs form easily (zero or small gaps) are unfailingly the most highly connected ones, also characterized by weak local clustering. Remarkably, a systematic analysis on a large database of enzyme structures reveals that amino-acid residues involved in enzymatic activity tend to be located in such regions. This finding reinforces the idea that localised modes of nonlinear origin may play an important biological role, e.g. by providing a ready channel for energy storage and/or contributing to lower energy barriers of chemical reactions.

q-bio.BM↗