Electrostatic Topology Research Articles

Improving the Precision of Calibrating a Large Low-background Proportional Counter

The study of low-yield effects requires not only good quality of the original data but also puts high requirements for their processing procedures to increase the efficiency of the selection of useful events. The exploiting of the large cylindrical proportional counter’s electrostatic topology allows improving the extrapolation of information about the primary ionization of a multipoint event. Long-term calibration measurements with an external 109Cd-source allowed the development of a new method for analyzing the pulse shape from a sizeable proportional counter. Optimized analysis of the current’s pulse shape from the electron cloud of primary ionization in the counter improved the resolution and energy calibration. As a result, the efficiency of selecting useful events was increased by 25%.

Structural mechanisms of interaction of cyanolcrylates with plant tubulin

Structural mechanisms underlying the specific binding of cyanoacrylate compounds with tubulin of higher plants have been studied by example of interaction of ethyl-(2Z)-3-amino-2-cyano-4-ethylhex-2-enoate (CA1) and isopropyl-(2Z)-3-amino-2-cyano-4-ethylhex-2-enoate (CA2) with Arabidopsis thaliana alpha-tubulin. It was revealed that the cyano group of cyanoacrylates is a functional analog of the nitrile group, which determines the processes of specific interaction with plant tubulin for dinitroaniline compounds. Based on the data of spatial structure fluctuations, dynamics of hydrogen bonds and interaction energy of the CA1 and CA2, the most probable binding mode for these compounds with plant alpha-tubulin was identified and appropriate site of interaction was characterized. Seven out of 10 residues composing this site (Gln-133, Asn-249, Val-250, Asp-251, Val-252, Asn-253 and Glu-254) are obligatory components of the dinitroanilines' binding site on the plant alpha-tubulin surface. Thus, the binding site on the alpha-tubulin surface characterized by us is able to recognize and specifically bind the substances which are cardinally different by their chemical nature and have no common pharmacophore groups, under the condition of a certain similarity of their electrostatic topology.

Surface properties of adipocyte lipid-binding protein: Response to lipid binding, and comparison with homologous proteins.

Adipocyte lipid-binding protein (ALBP) is one of a family of intracellular lipid-binding proteins (iLBPs) that bind fatty acids, retinoids, and other hydrophobic ligands. The different members of this family exhibit a highly conserved three-dimensional structure; and where structures have been determined both with (holo) and without (apo) bound lipid, observed conformational changes are extremely small (Banaszak, et al., 1994, Adv. Prot. Chem. 45, 89; Bernlohr, et al., 1997, Annu. Rev. Nutr. 17, 277). We have examined the electrostatic, hydrophobic, and water accessible surfaces of ALBP in the apo form and of holo forms with a variety of bound ligands. These calculations reveal a number of previously unrecognized changes between apo and holo ALBP, including: 1) an increase in the overall protein surface area when ligand binds, 2) expansion of the binding cavity when ligand is bound, 3) clustering of individual residue exposure increases in the area surrounding the proposed ligand entry portal, and 4) ligand-binding dependent variation in the topology of the electrostatic potential in the area surrounding the ligand entry portal. These focused analyses of the crystallographic structures thus reveal a number of subtle but consistent conformational and surface changes that might serve as markers for differential targeting of protein-lipid complexes within the cell. Most changes are consistent from ligand to ligand, however there are some ligand-specific changes. Comparable calculations with intestinal fatty-acid-binding protein and other vertebrate iLBPs show differences in the electrostatic topology, hydrophobic topology, and in localized changes in solvent exposure near the ligand entry portal. These results provide a basis toward understanding the functional and mechanistic differences among these highly structurally homologous proteins. Further, they suggest that iLBPs from different tissues exhibit one of two predominant end-state structural distributions of the ligand entry portal.