SAnDReS 2.0: Development of machine-learning models to explore the scoring function space.

Classical scoring functions may exhibit low accuracy in determining ligand binding affinity for proteins. The availability of both protein-ligand structures and affinity data make it possible to develop machine-learning models focused on specific protein systems with superior predictive performance. Here, we report a new methodology named SAnDReS that combines AutoDock Vina 1.

Identification of transcriptional modules linked to the drought response of Brassica napus during seed development and their mitigation by early biotic stress.

In order to capture the drought impacts on seed quality acquisition in Brassica napus and its potential interaction with early biotic stress, seeds of the 'Express' genotype of oilseed rape were characterized from late embryogenesis to full maturity from plants submitted to reduced watering (WS) with or without pre-occurring inoculation by the telluric pathogen Plasmodiophora brassicae (Pb + WS or Pb, respectively), and compared to control conditions (C). Drought as a single constraint led to significantly lower accumulation of lipids, higher protein content and reduced longevity of the WS-treated seeds. In contrast, when water shortage was preceded by clubroot infection, these phenotypic differences were completely abolished despite the upregulation of the drought sensor RD20.

Structural and physical basis for the elasticity of elastin.

Elastin function is to endow vertebrate tissues with elasticity so that they can adapt to local mechanical constraints. The hydrophobicity and insolubility of the mature elastin polymer have hampered studies of its molecular organisation and structure-elasticity relationships. Nevertheless, a growing number of studies from a broad range of disciplines have provided invaluable insights, and several structural models of elastin have been proposed.

SGPocket: A New Graph Convolutional Neural Network for Ligand-protein Binding Site Prediction.

Background: Drug research is a long process, taking more than 10 years and requiring considerable financial resources. Therefore, researchers and industrials aim to reduce time and cost. Thus, they use computational simulations like molecular docking to explore huge databases of compounds and extract the most promising ones for further tests.

Challenging level of rigid-body approach involving numerical elements (CHLORAINE) applied to repeated elastin peptides.

Elastic proteins and derived biomaterials contain numerous tandemly repeated peptides along their sequences, ranging from a few copies to hundreds. These repetitions are responsible for their biochemical, biological and biomechanical properties. These sequences are considered to be intrinsically disordered, and the variations in their behavior are actually mainly due to their high flexibility and lack of stable secondary structures originating from their unique amino acid sequences.

Highlighting the hygroscopic capacities of apiogalacturonans.

To meet the needs of dehydrated skin, molecules with a high hygroscopic potential are necessary to hydrate it effectively and durably. In this context, we were interested in pectins, and more precisely in apiogalacturonans (AGA), a singular one that is currently only found in a few species of aquatic plants. As key structures in water regulation of these aquatic plants and thanks to their molecular composition and conformations, we hypothesized that they could have beneficial role for skin hydration.

Recent progress in molecular genetics and omics-driven research in seed biology.

Elucidating the mechanisms that control seed development, metabolism, and physiology is a fundamental issue in biology. Michel Caboche had long been a catalyst for seed biology research in France up until his untimely passing away last year. To honour his memory, we have updated a review written under his coordination in 2010 entitled "Arabidopsis seed secrets unravelled after a decade of genetic and omics-driven research".

Modelling and Simulations of Extracellular Glycoproteins.

While the knowledge of protein structure and function has seen vast advances in previous decades, the understanding of how their posttranslational modifications, such as glycosylations, influence their structure and function remains poor. However, advances in in silico methodologies to study glycosylations in recent past have enabled us to study this and understand the role of glycosylations in protein structure and function in ways that would not be possible by conventional experimental methods. In this chapter, we will demonstrate how to leverage these methodologies to study glycoproteins and their structural and dynamic properties using molecular modelling techniques.

Differential MMP-14 targeting by biglycan, decorin, fibromodulin, and lumican unraveled by in silico approach.

Small leucine-rich proteoglycans (SLRPs) are major regulators of extracellular matrix assembly and cell signaling. Lumican, a member of the SLRPs family, and its derived peptides were shown to possess antitumor activity by interacting directly with the catalytic domain of MMP-14 leading to the inhibition of its activity. The aim of the present report was to characterize by in silico three-dimensional (3D) modeling the structure and the dynamics of four SLRPs including their core protein and their specific polysaccharide chains to assess their capacity to bind to MMP-14 and to regulate its activity.

How molecular modelling can better broaden the understanding of glycosylations.

Glycosylations are among the most ubiquitous post-translational modifications (PTMs) in proteins, and the effects of their perturbations are seen in various diseases such as cancers, diabetes and arthritis to name a few. Yet they remain one of the most enigmatic aspects of protein structure and function. On the other hand, molecular modelling techniques have been rapidly bridging this knowledge gap since the last decade.

Early Alterations of Intra-Mural Elastic Lamellae Revealed by Synchrotron X-ray Micro-CT Exploration of Diabetic Aortas.

Diabetes is a major concern of our society as it affects one person out of 11 around the world. Elastic fiber alterations due to diabetes increase the stiffness of large arteries, but the structural effects of these alterations are poorly known. To address this issue, we used synchrotron X-ray microcomputed tomography with in-line phase contrast to image in three dimensions C57Bl6J (control) and db/db (diabetic) mice with a resolution of 650 nm/voxel and a field size of 1.

Multiscale modelling of the extracellular matrix.

The extracellular matrix is a complex three-dimensional network of molecules that provides cells with a complex microenvironment. The major constituents of the extracellular matrix such as collagen, elastin and associated proteins form supramolecular assemblies contributing to its physicochemical properties and organization. The structure of proteins and their supramolecular assemblies such as fibrils have been studied at the atomic level (e.

Plant monounsaturated fatty acids: Diversity, biosynthesis, functions and uses.

Monounsaturated fatty acids are straight-chain aliphatic monocarboxylic acids comprising a unique carbon‑carbon double bond, also termed unsaturation. More than 50 distinct molecular structures have been described in the plant kingdom, and more remain to be discovered. The evolution of land plants has apparently resulted in the convergent evolution of non-homologous enzymes catalyzing the dehydrogenation of saturated acyl chain substrates in a chemo-, regio- and stereoselective manner.

Differential MMP-14 Targeting by Lumican-Derived Peptides Unraveled by In Silico Approach.

Lumican, a small leucine-rich proteoglycan (SLRP) of the extracellular matrix (ECM), displays anti-tumor properties through its direct interaction with MMP-14. Lumican-derived peptides, such as lumcorin (17 amino acids) or L9M (10 amino acids), are able to inhibit the proteolytic activity of MMP-14 and melanoma progression. This work aimed to visualize the interactions of lumican-derived peptides and MMP-14.

Machine-learning methods for ligand-protein molecular docking.

Artificial intelligence (AI) is often presented as a new Industrial Revolution. Many domains use AI, including molecular simulation for drug discovery. In this review, we provide an overview of ligand-protein molecular docking and how machine learning (ML), especially deep learning (DL), a subset of ML, is transforming the field by tackling the associated challenges.

Effects of changes in glycan composition on glycoprotein dynamics: example of N-glycans on insulin receptor.

Glycosylation is among the most common post-translational modifications in proteins, although it is observed in only about 10% of all the protein structures in protein data bank (PDB). Modifications of sugar composition in glycoproteins profoundly impact the overall physiology of the organism. One such example is the development of insulin resistance, which has been attributed to the removal of sialic acid residues from N-glycans of insulin receptor (IR) from various experimental studies.

AMIDE v2: High-Throughput Screening Based on AutoDock-GPU and Improved Workflow Leading to Better Performance and Reliability.

Molecular docking is widely used in computed drug discovery and biological target identification, but getting fast results can be tedious and often requires supercomputing solutions. AMIDE stands for AutoMated Inverse Docking Engine. It was initially developed in 2014 to perform inverse docking on High Performance Computing.

Acyl-Acyl Carrier Protein Desaturases and Plant Biotic Interactions.

Interactions between land plants and other organisms such as pathogens, pollinators, or symbionts usually involve a variety of specialized effectors participating in complex cross-talks between organisms. Fatty acids and their lipid derivatives play important roles in these biological interactions. While the transcriptional regulation of genes encoding acyl-acyl carrier protein (ACP) desaturases appears to be largely responsive to biotic stress, the different monounsaturated fatty acids produced by these enzymes were shown to take active part in plant biotic interactions and were assigned with specific functions intrinsically linked to the position of the carbon-carbon double bond within their acyl chain.

Molecular Control of Oil Metabolism in the Endosperm of Seeds.

In angiosperm seeds, the endosperm develops to varying degrees and accumulates different types of storage compounds remobilized by the seedling during early post-germinative growth. Whereas the molecular mechanisms controlling the metabolism of starch and seed-storage proteins in the endosperm of cereal grains are relatively well characterized, the regulation of oil metabolism in the endosperm of developing and germinating oilseeds has received particular attention only more recently, thanks to the emergence and continuous improvement of analytical techniques allowing the evaluation, within a spatial context, of gene activity on one side, and lipid metabolism on the other side. These studies represent a fundamental step toward the elucidation of the molecular mechanisms governing oil metabolism in this particular tissue.

AG-9, an Elastin-Derived Peptide, Increases In Vitro Oral Tongue Carcinoma Cell Invasion, through an Increase in MMP-2 Secretion and MT1-MMP Expression, in a RPSA-Dependent Manner.

Oral tongue squamous cell carcinoma is one of the most prevalent head and neck cancers. During tumor progression, elastin fragments are released in the tumor microenvironment. Among them, we previously identified a nonapeptide, AG-9, that stimulates melanoma progression in vivo in a mouse melanoma model.

Transmembrane Peptides as a New Strategy to Inhibit Neuraminidase-1 Activation.

Sialidases, or neuraminidases, are involved in several human disorders such as neurodegenerative, infectious and cardiovascular diseases, and cancers. Accumulative data have shown that inhibition of neuraminidases, such as NEU1 sialidase, may be a promising pharmacological target, and selective inhibitors of NEU1 are therefore needed to better understand the biological functions of this sialidase. In the present study, we designed interfering peptides (IntPep) that target a transmembrane dimerization interface previously identified in human NEU1 that controls its membrane dimerization and sialidase activity.

Docking of acetyl-CoA carboxylase to the plastid envelope membrane attenuates fatty acid production in plants.

In plants, light-dependent activation of de novo fatty acid synthesis (FAS) is partially mediated by acetyl-CoA carboxylase (ACCase), the first committed step for this pathway. However, it is not fully understood how plants control light-dependent FAS regulation to meet the cellular demand for acyl chains. We report here the identification of a gene family encoding for three small plastidial proteins of the envelope membrane that interact with the α-carboxyltransferase (α-CT) subunit of ACCase and participate in an original mechanism restraining FAS in the light.