Search results for "Models"

Synthesis, in vitro activity, and three-dimensional quantitative structure-activity relationship of novel hydrazine inhibitors of human vascular adhe…

2010

Vascular adhesion protein-1 (VAP-1) belongs to the semicarbazide-sensitive amine oxidases (SSAOs) that convert amines into aldehydes. SSAOs are distinct from the mammalian monoamine oxidases (MAOs), but their substrate specificities are partly overlapping. VAP-1 has been proposed as a target for anti-inflammatory drug therapy because of its role in leukocyte adhesion to endothelium. Here, we describe the synthesis and in vitro activities of novel series of VAP-1 selective inhibitors. In addition, the molecular dynamics simulations performed for VAP-1 reveal that the movements of Met211, Ser496, and especially Leu469 can enlarge the ligand-binding pocket, allowing larger ligands than those s…

Pyrazolo[3,4-d]pyrimidine derivatives as COX-2 selective inhibitors: synthesis and molecular modelling studies.

2009

The pyrazolo[3,4-d]pyrimidine system shows a multitude of interesting pharmacological properties. Owing to the potential anti-inflammatory activity of 5-benzamido-pyrazolo[3,4-d]pyrimidin- 4-one derivatives and considering the easy synthesis of this class of compounds, a set of new 5- benzamido-1H-pyrazolo[3,4-d]pyrimidin-4-ones has been prepared in 42-80% yields by reacting 5- aminopyrazole-4(N-benzoyl)carbohydrazide derivatives and the opportune triethylorthoesters. Compounds 8a, b, 10a–d, and 11a, b revealed a superior inhibitory profile against COX-2, when compared to that of reference standards NS398 and indomethacin. Molecular modelling studies confirmed the obtained biological result…

Calorimetric Behavior of Phosphatidylcholine/Phosphatidylethanolamine Bilayers is Compatible with the Superlattice Model

2012

Differential scanning calorimetry was used to study the phase behavior of binary lipid bilayers consisting of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of varying acyl chain length. A two-state transition model was used to resolve the individual transition components, and the two-state transition enthalpy, the relative enthalpy, and the transition temperature of each component were plotted as a function of composition. Intriguingly, abrupt changes in these thermodynamic parameters were observed at or close to many "critical" X(PE) values predicted by the superlattice model proposing that phospholipids with different headgroups tend to adopt regular rather than random latera…

String kernels and high-quality data set for improved prediction of kinked helices in α-helical membrane proteins.

2011

The reasons for distortions from optimal α-helical geometry are widely unknown, but their influences on structural changes of proteins are significant. Hence, their prediction is a crucial problem in structural bioinformatics. For the particular case of kink prediction, we generated a data set of 132 membrane proteins containing 1014 manually labeled helices and examined the environment of kinks. Our sequence analysis confirms the great relevance of proline and reveals disproportionately high occurrences of glycine and serine at kink positions. The structural analysis shows significantly different solvent accessible surface area mean values for kinked and nonkinked helices. More important, …

Cyclodextrin and Adamantane Host-Guest Interactions of Modified Hyperbranched Poly(ethylene imine) as Mimetics for Biological Membranes

2011

Magnesium Exchanged Zirconium Metal−Organic Frameworks with Improved Detoxification Properties of Nerve Agents

2019

UiO-66, MOF-808 and NU-1000 metal-organic frameworks exhibit a differentiated reactivity toward [Mg(OMe)2(MeOH)2]4 related to their pore accessibility. Microporous UiO-66 remains unchanged while mesoporous MOF-808 and hierarchical micro/mesoporous NU-1000 materials yield doped systems containing exposed MgZr5O2(OH)6 clusters in the mesoporous cavities. This modification is responsible for a remarkable enhancement of the catalytic activity toward the hydrolytic degradation of P-F and P-S bonds of toxic nerve agents, at room temperature, in unbuffered aqueous solutions.

Molecular volumes and surfaces of biomacromolecules via GEPOL: A fast and efficient algorithm

1990

A triangular tesselation approach to build up surfaces has been adapted to the study of biomolecules. By using a data-coded generic pentakisdodecahedron each atom is assigned a particular sphere whose radii are chosen according to any suitable property. Different types of surfaces have been adapted to this method: van der Waals, surface accessible, and Richard's molecular surface. A simple method is used to eliminate all triangles found at the intersection volume of the atomic spheres and a fast algorithm is employed to calculate the area of the envelope surface and the volume therein. The data about the surface are given by the coordinates of the center of each triangle, elementary surface…

Interfacial activation-based molecular bioimprinting of lipolytic enzymes

1995

Interfacial activation-based molecular (bio)-imprinting (IAMI) has been developed to rationally improve the performance of lipolytic enzymes in nonaqueous environments. The strategy combinedly exploits (i) the known dramatic enhancement of the protein conformational rigidity in a water-restricted milieu and (ii) the reported conformational changes associated with the activation of these enzymes at lipid-water interfaces, which basically involves an increased substrate accessibility to the active site and/or an induction of a more competent catalytic machinery. Six model enzymes have been assayed in several model reactions in nonaqueous media. The results, rationalized in light of the presen…

Functional competition within a membrane: Lipid recognition vs. transmembrane helix oligomerization

2015

Abstract Binding of specific lipids to large, polytopic membrane proteins is well described, and it is clear that such lipids are crucial for protein stability and activity. In contrast, binding of defined lipid species to individual transmembrane helices and regulation of transmembrane helix monomer–oligomer equilibria by binding of distinct lipids is a concept, which has emerged only lately. Lipids bind to single-span membrane proteins, both in the juxta-membrane region as well as in the hydrophobic membrane core. While some interactions counteract transmembrane helix oligomerization, in other cases lipid binding appears to enhance oligomerization. As reversible oligomerization is involve…

Comprehensive analysis of a Vibrio parahaemolyticus strain extracellular serine protease VpSP37

2015

Proteases play an important role in the field of tissue dissociation combined with regenerative medicine. During the years new sources of proteolytic enzymes have been studied including proteases from different marine organisms both eukaryotic and prokaryotic. Herein we have purified a secreted component of an isolate of Vibrio parahaemolyticus, with electrophoretic mobilities corresponding to 36 kDa, belonging to the serine proteases family. Sequencing of the N-terminus enabled the in silico identification of the whole primary structure consisting of 345 amino acid residues with a calculated molecular mass of 37.4 KDa. The purified enzyme, named VpSP37, contains a Serine protease domain be…