Computational study of ligand binding in lipid transfer proteins: Structures, interfaces, and free energies of protein-lipid complexes

Plant nonspecific lipid transfer proteins (nsLTPs) bind a wide variety of lipids, which allows them to perform disparate functions. Recent reports on their multifunctionality in plant growth processes have posed new questions on the versatile binding abilities of these proteins. The lack of binding specificity has been customarily explained in qualitative terms on the basis of a supposed structural flexibility and nonspecificity of hydrophobic protein-ligand interactions. We present here a computational study of protein-ligand complexes formed between five nsLTPs and seven lipids bound in two different ways in every receptor protein. After optimizing geometries inmolecular dynamics calculations, we computed Poisson- Boltzmann electrostatic potentials, solvation energies, properties of the protein-ligand interfaces, and estimates of binding free energies of the resulting complexes. Our results provide the first quantitative information on the ligand abilities of nsLTPs, shed new light into protein-lipid interactions, and reveal new features which supplement commonly held assumptions on their lack of binding specificity.

Modeling iron-catecholates binding to NGAL protein

Neutrophil gelatinase associated lipocalin (NGAL) protein is attracting a great interest because of its antibacterial properties played upon modulating iron content in competition against iron acquisition processes developed by pathogenic bacteria that bind selective ferric iron chelators (siderophores). Besides its known high affinity to enterobactin, the most important siderophore, it has been recently shown that NGAL is able to bind Fe(III) coordinated by catechols. The selective binding of Fe(III)-catechol ligands to NGAL is here studied by using iron coordination structures with one, two, and three catecholate ligands. By means of a computational approach that consists of B3LYP/6-311G(d,p) quantum calculations for geometries, electron properties and electrostatic potentials of ligands, protein–ligand flexible docking calculations, analyses of protein–ligand interfaces, and Poisson–Boltzmann electrostatic potentials for proteins, we study the binding of iron catecholate ligands to NGAL as a central member of the lipocalin family of proteins. This approach provides a modeling basis for exploring in silico the selective binding of iron catecholates ligands giving a detailed picture of their interactions in terms of electrostatic effects and a network of hydrogen bonds in the protein binding pocket.

The theory of electrostatic probes in strong magnetic fields : Thesis submitted to the Faculty of The Graduate School of the University of Colorado for the Degree Doctor of Philosophy Department of Aerospace Engineering Science

A theory is developed of an electrostatic probe in a fully-ionized plasma in the presence of a strong magnetic field. The ratio of electron Larmor radius to probe transverse dimension is assumed to be small. Poisson's equation, together with kinetic equations for ions and electrons are considered. An asymptotic perturbation method of multiple scales is used by considering the characteristic lengths appearing in the problem. The leading behavior of the solution is found. The results obtained appear to apply to weaker fields also, agreeing with the solutions known in the limit of no magnetic field. The range of potentials for wich results are presented is limited. The basic effects produced by the field are a depletion of the plasma near the probe and a non-monotonic potential surrounding the probe. The ion saturation current is not changed but changes appear in both the floating potential Vf and the slope of the current-voltage diagram at Vf. The transition region extends beyond the space potential Vs,at wich point the current is largely reduced. The diagram does not have an exponential form in this region as commonly assumed. There exists saturation in electron collection. The extent to which the plasma is disturbed is determined. A cylindrical probe has no solution because of a logarithmic singularity at infinity. Extensions of the theory are considered.