General Trends of the Antibody VHs Domain Dynamics.

Conformational flexibility plays an essential role in antibodies' functional and structural stability. They facilitate and determine the strength of antigen-antibody interactions. Camelidae express an interesting subtype of single-chain antibody, named Heavy Chain only Antibody.

Quality assessment of VH models.

Heavy Chain Only Antibodies are specific to Camelid species. Despite the lack of the light chain variable domain, their heavy chain variable domain (VH) domain, named VH or nanobody, has promising potential applications in research and therapeutic fields. The structural study of VH is therefore of great interest.

VH Structural Modelling Approaches: A Critical Review.

VH, i.e., VH domains of camelid single-chain antibodies, are very promising therapeutic agents due to their significant physicochemical advantages compared to classical mammalian antibodies.

Piperidinyl-embeded chalcones possessing anti PI3Kδ inhibitory properties exhibit anti-atopic properties in preclinical models.

Phosphatidylinositide 3-kinases (PI3Ks) are widely expressed enzymes involved in membrane signalization pathways. Attempts to administer inhibitors with broad activity against different isoforms have failed due to toxicity. Conversely the PI3Kδ isoform is much more selectively expressed, enabling therapeutic targeting of this isoform.

Identification of Inhibitors for the Lutheran Blood Group Glycoprotein - Laminin 511/521 Interaction by Molecular Modelling and Simulation Techniques.

Background: Drepanocytosis is a genetic blood disorder characterized by red blood cells that assume an abnormal, rigid, sickle shape. In the pathogenesis of vaso-occlusive crises of sickle cell disease, red blood cells bind to the endothelium and promote vaso-occlusion. At the surface of these sickle red blood cells, the overexpressed protein Lutheran strongly interacts with the Laminin 511/521.

Structure-affinity properties of a high-affinity ligand of FKBP12 studied by molecular simulations of a binding intermediate.

With a view to explaining the structure-affinity properties of the ligands of the protein FKBP12, we characterized a binding intermediate state between this protein and a high-affinity ligand. Indeed, the nature and extent of the intermolecular contacts developed in such a species may play a role on its stability and, hence, on the overall association rate. To find the binding intermediate, a molecular simulation protocol was used to unbind the ligand by gradually decreasing the biasing forces introduced.

Classical force field parameters for two high-affinity ligands of FKBP12.

FKBP12 is an important target in the treatment of transplant rejection and is also a promising target for cancer and neurodegenerative diseases. We determined for two ligands of nanomolar affinity the set of parameters in the CHARMM force field. The fitting procedure was based on reproducing the quantum chemistry data (distances, angles, and energies).

Molecular Dynamics Simulations of a Binding Intermediate between FKBP12 and a High-Affinity Ligand.

We characterized a binding intermediate between the protein FKBP12 and one of its high-affinity ligands by means of molecular dynamics simulations. In such an intermediate, which is expected to form at the end-point of the bimolecular diffusional search, short-range interactions between the molecular partners may play a role in the specificity of recognition as well as in the association rate. Langevin dynamics simulations were carried out to generate the intermediate by applying an external biasing force to unbind the ligand from the protein.

Liquid crystalline metal-free phthalocyanines designed for charge and exciton transport.

A joint theoretical and experimental study of the electronic and structural properties of liquid crystalline metal-free phthalocyanines bearing a strong potential for charge and exciton transport has been performed. The synthesis of such compounds has been triggered by quantum chemical calculations showing that: (i) hole transport is favored in metal-free phthalocyanines by their extremely low reorganization energy (0.045 eV) and large electronic splittings; and (ii) the efficiency of energy transfer along the one-dimensional discotic stacks is weakly affected by rotational disorder due to the two-dimensional character of the molecules.

Molecular dynamics simulations of nanocomposites based on poly(epsilon-caprolactone) grafted on montmorillonite clay.

Intercalated and exfoliated models of polymer nanocomposites based on poly(epsilon-caprolactone) and functionalized montmorillonite clay are studied by means of molecular dynamics simulations. Intercalated and exfoliated models are considered for probing the structural characteristics of the corresponding nanocomposites prepared by melt intercalation and in situ polymerization, respectively. In the exfoliated system, the organization of the polymer chains onto the clay surface is examined in terms of the density profiles and the order parameter function.

Chiral amphiphilic self-assembled alpha,alpha'-linked quinque-, sexi-, and septithiophenes: synthesis, stability and odd-even effects.

The synthesis, characterization, and self-assembly in butanol of a series of well-defined alpha,alpha'-linked quinqui-, sexi-, and septithiophenes substituted, via ester links at their termini, by chiral oligo(ethylene oxide) chains carrying an alpha, beta, delta, and epsilon methyl, respectively, are reported. Studies of the self-assembly of these molecules using UV/visible absorption, luminescence, and circular dichroism spectroscopies reveal, for the sexithiophene case, that the magnitude of the observed Cotton effect in the aggregates diminishes progressively as the chiral substituent is moved away from the thiophene segment. The stability of the assemblies increases with the length of the oligothiophene and as the substituent chiral unit is moved away from the aromatic core, being greatest for the unsubstituted case.

Construction of a 3D model of CP12, a protein linker.

The chloroplast protein CP12 is known to play a leading role in a complex formation with the enzymes GAPDH and PRK. As a preliminary step towards the understanding of the complex formation mechanism and the exact role of this protein linker, a comparative modelling of the CP12 protein of the green alga Chlamydomonas reinhardtii was performed. Because of the very few structural information and poor template similarities, the derivation of the model consisted in an iterative trial-and-error procedure using the comparative modelling program MODELLER, the following three structure validation programs PROCHECK, PROSA, and WHATIF, and molecular mechanics energy refinement of the model using the program CHARMM.