The hinge-engineered IgG1-IgG3 hybrid subclass IgGh potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies.

Streptococcus pyogenes can cause invasive disease with high mortality despite adequate antibiotic treatments. To address this unmet need, we have previously generated an opsonic IgG1 monoclonal antibody, Ab25, targeting the bacterial M protein. Here, we engineer the IgG2-4 subclasses of Ab25.

Cysteine hyperoxidation rewires communication pathways in the nucleosome and destabilizes the dyad.

Gene activity is tightly controlled by reversible chemical modifications called epigenetic marks, which are of various types and modulate gene accessibility without affecting the DNA sequence. Despite an increasing body of evidence demonstrating the role of oxidative-type modifications of histones in gene expression regulation, there remains a complete absence of structural data at the atomistic level to understand the molecular mechanisms behind their regulatory action. Owing to μs time-scale MD simulations and protein communication networks analysis, we describe the impact of histone H3 hyperoxidation (i.

Exploring a Structural Data Mining Approach to Design Linkers for Head-to-Tail Peptide Cyclization.

Peptides have recently regained interest as therapeutic candidates, but their development remains confronted with several limitations including low bioavailability. Backbone head-to-tail cyclization, i.e.

Bat coronaviruses related to SARS-CoV-2 and infectious for human cells.

The animal reservoir of SARS-CoV-2 is unknown despite reports of SARS-CoV-2-related viruses in Asian Rhinolophus bats, including the closest virus from R. affinis, RaTG13 (refs. ), and pangolins.

Computational and biochemical analysis of type IV pilus dynamics and stability.

Type IV pili (T4P) are distinctive dynamic filaments at the surface of many bacteria that can rapidly extend and retract and withstand strong forces. T4P are important virulence factors in many human pathogens, including Enterohemorrhagic Escherichia coli (EHEC). The structure of the EHEC T4P has been determined by integrating nuclear magnetic resonance (NMR) and cryo-electron microscopy data.

Automatic Bayesian Weighting for SAXS Data.

Small-angle X-ray scattering (SAXS) experiments are important in structural biology because they are solution methods, and do not require crystallization of protein complexes. Structure determination from SAXS data, however, poses some difficulties. Computation of a SAXS profile from a protein model is expensive in CPU time.

Predicting substitutions to modulate disorder and stability in coiled-coils.

Background: Coiled-coils are described as stable structural motifs, where two or more helices wind around each other. However, coiled-coils are associated with local mobility and intrinsic disorder. Intrinsically disordered regions in proteins are characterized by lack of stable secondary and tertiary structure under physiological conditions in vitro.

GEMME: A Simple and Fast Global Epistatic Model Predicting Mutational Effects.

The systematic and accurate description of protein mutational landscapes is a question of utmost importance in biology, bioengineering, and medicine. Recent progress has been achieved by leveraging on the increasing wealth of genomic data and by modeling intersite dependencies within biological sequences. However, state-of-the-art methods remain time consuming.

"Infostery" analysis of short molecular dynamics simulations identifies highly sensitive residues and predicts deleterious mutations.

Characterizing a protein mutational landscape is a very challenging problem in Biology. Many disease-associated mutations do not seem to produce any effect on the global shape nor motions of the protein. Here, we use relatively short all-atom biomolecular simulations to predict mutational outcomes and we quantitatively assess the predictions on several hundreds of mutants.

DaReUS-Loop: accurate loop modeling using fragments from remote or unrelated proteins.

Despite efforts during the past decades, loop modeling remains a difficult part of protein structure modeling. Several approaches have been developed in the framework of crystal structures. However, for homology models, the modeling of loops is still far from being solved.

Dissecting protein architecture with communication blocks and communicating segment pairs.

Background: Proteins adapt to environmental conditions by changing their shape and motions. Characterising protein conformational dynamics is increasingly recognised as necessary to understand how proteins function. Given a conformational ensemble, computational tools are needed to extract in a systematic way pertinent and comprehensive biological information.