Viscoelastic Properties of p-n Alkyl Benzoic Acid Mesogens

Abstract: Dynamic rheological behaviour, such as storage modulus (G') and loss modulus (G'') are measured as a function of frequency at different temperatures in nematic region and also studied linear viscoelastic behaviour of p-n alkyl benzoic acid (nBA) mesogens. Different zones are exhibited by the samples, -a plateau zone at low frequencies, a transition zone at high frequencies and a zone entire plateau showing for crossover frequencies and relaxation times. The dependence of the elastic (G′) and loss (G′′) moduli on frequency is strong. The observed crossover points of G′, G′′ in the study of frequency range is indicating that nematic phase of nBA has behaved like both viscoelastic solid and liquid for small deformations (<1% strain). A typical shear thinning behaviour of viscosity has been displayed when the samples are subjected to shearing at a constant temperature. This typical shear thinning has approached slowly moving to Newtonian viscosity at high shear rates showing progressive development of nematic molecular orientation along flow direction on increasing shear rate. Rheological behaviour of the nBA nematic phases is in general consistent like the other reported compounds except the one thermotropic liquid crystals. The higher shear force and lower viscosity ratio is observed in these compounds in which pentyl benzoic acid has high ratio indicating the high molecular orientation may be due to low chain entanglement

Water-Restructuring Mutations Can Reverse the Thermodynamic Signature of Ligand Binding to Human Carbonic Anhydrase

This study uses mutants of human carbonic anhydrase (HCAII) to examine how changes in the organization of water within a binding pocket can alter the thermodynamics of protein–ligand association. Results from calorimetric, crystallographic, and theoretical analyses suggest that most mutations strengthen networks of water-mediated hydrogen bonds and reduce binding affinity by increasing the enthalpic cost and, to a lesser extent, the entropic benefit of rearranging those networks during binding. The organization of water within a binding pocket can thus determine whether the hydrophobic interactions in which it engages are enthalpy-driven or entropy driven. Our findings highlight a possible asymmetry in protein–ligand association by suggesting that, within the confines of the binding pocket of HCAII, binding events associated with enthalpically favorable rearrangements of water are stronger than those associated with entropically favorable ones.Chemistry and Chemical Biolog

Interactions between Hofmeister Anions and the Binding Pocket of a Protein

This paper uses the binding pocket of human carbonic anhydrase II (HCAII, EC 4.2.1.1) as a tool to examine the properties of Hofmeister anions that determine (i) where, and how strongly, they associate with concavities on the surfaces of proteins and (ii) how, upon binding, they alter the structure of water within those concavities. Results from X-ray crystallography and isothermal titration calorimetry show that most anions associate with the binding pocket of HCAII by forming inner-sphere ion pairs with the Zn2+ cofactor. In these ion pairs, the free energy of anion–Zn2+ association is inversely proportional to the free energetic cost of anion dehydration; this relationship is consistent with the mechanism of ion pair formation suggested by the “law of matching water affinities”. Iodide and bromide anions also associate with a hydrophobic declivity in the wall of the binding pocket. Molecular dynamics simulations suggest that anions, upon associating with Zn2+, trigger rearrangements of water that extend up to 8 Å away from their surfaces. These findings expand the range of interactions previously thought to occur between ions and proteins by suggesting that (i) weakly hydrated anions can bind complementarily shaped hydrophobic declivities, and that (ii) ion-induced rearrangements of water within protein concavities can (in contrast with similar rearrangements in bulk water) extend well beyond the first hydration shells of the ions that trigger them. This study paints a picture of Hofmeister anions as a set of structurally varied ligands that differ in size, shape, and affinity for water and, thus, in their ability to bind to—and to alter the charge and hydration structure of—polar, nonpolar, and topographically complex concavities on the surfaces of proteins.Chemistry and Chemical Biolog

Identification of the thistle milk component Silibinin(A) and Glutathione-disulphide as potential inhibitors of the pancreatic lipase: Potential implications on weight loss

This work has been supported by Ministerio de Ciencia e Innovacion de Espana (under project RTI2018101309BC21) , by the Fundacion Seneca del Centro de Coordinacion de la Investigacion de la Region de Murcia (under Project 20988/PI/18) and by a grant from Ministerio de Economia y Competitividad de Espana (CTQ201787974R) . This research was partially supported by the supercomputing infrastructure of Poznan Supercomputing Centre, and by the einfrastructure program of the Research Council of Norway, and the supercomputer centre of UiTthe Arctic University of Norway. The authors also thankfully acknowledge the computer resources and the technical support provided by the Plataforma Andaluza de Bioinformatica of the University of Malaga. Powered@NLHPC: This research was partially supported by the supercomputing infrastructure of the NLHPC (ECM02)Peripheral targets like pancreatic-lipase appear to be the most suitable pharmacological alternative for obesity, as with orlistat, although its adverse effects limit its use. Therefore, the aim of this work was to identify new natural compounds able to inhibit pancreatic-lipase in an in vitro model. The DrugBank database was used to perform docking calculations. The best fitting-score compounds were further evaluated in vitro. Our data revealed that glutathione-disulphide (GSSG) and silibinin(A) inhibit pancreatic-lipase. This was confirmed by measuring hydrolysis in an emulsion model, obtaining that the suppression of lipid digestion by silibinin(A) was higher than that of GSSG and close to the effect of orlistat. Combined analysis established the existence of different inhibition mechanisms for each compound. In summary, silibinin(A) and GSSG inhibited pancreatic-lipase and, therefore, may be served as promise natural compounds to face with obesity. Further studies comprise the next step to fully validate the suitability of these compounds.Spanish Government RTI2018-101309-B-C21Fundacion Seneca 20988/PI/18Ministerio de Economia y Competitividad de Espana CTQ2017-87974-RSupercomputing infrastructure of Poznan Supercomputing CentreEinfrastructure program of the Research Council of NorwaySupercomputer centre of UiTthe Arctic University of NorwaySupercomputer centre of UiTthe Arctic University of Norwa

Trehalose Prevents Myoglobin Collapse and Preserves Its Internal Mobility

: A quantitative model, which involves diffusion on a temperature-dependent potential, is utilized to analyze the time-dependence of geminate CO recombination to sperm whale myoglobin in a trehalose glass and the accompanying spectral shifts. Most of the recombination is inhomogeneous. This is due to higher geminate reactivity rather than slower protein relaxation. A fraction of the hemes undergoes relaxation with a concomitant increase in the barrier height for recombination. The activation energy for conformational diffusion (relaxation) is considerably lower than in glycerol/water. "Protein collapse", manifested in glycerol/water by a decrease in the equilibrium conformational separation between the bound and deoxy states, is completely prevented in trehalose. We postulate that the high internal viscosity in glycerol/water is due to dehydration of the heme pocket. Trehalose prevents the escape of the few vital internal water molecules and thus preserves the internal labilit..

Aromatic–aromatic interactions database, A<SUP>2</SUP>ID: an analysis of aromatic π-networks in proteins

The geometrical arrangement of the aromatic rings of phenylalanine, tyrosine, tryptophan and histidine has been analyzed at a database level using the X-ray crystal structure of proteins from PDB in order to find out the aromatic–aromatic (π–π) networks in proteins and to understand how these aromatic rings are connected with each-other in a specific π–π network. A stringent examination of the 7848 proteins indicates that close to 89% of the proteins have occurrence of at least a network of 2π or a higher π–π network. The occurrence of π–π networks in various protein superfamilies based on SCOP, CATH and EC classifiers has also been probed in the present work. In general, we find that multidomain and membrane proteins as well as lyases show a more number of these networks. Analysis of the distribution of angle between planes of two proximal aromatic rings (ϕ) distribution indicates that at a larger cutoff distance (between centroid of two aromatic rings), above 5 Å, C–H⋯π interactions (T-shaped orientation) are more prevalent, while π–π interactions (stacked orientation) are more prevalent at a smaller cutoff distance. The connectivity patterns of π–π networks propose strong propensity of finding arrangement of aromatic residues as clusters rather than linear arrangement. We have also made a public domain database “Aromatic–Aromatic Interactions Database” (A2ID) comprising of all types of π–π networks and their connectivity pattern present in proteins. It can be accessed by url http://203.199.182.73/gnsmmg/databases/aidb/aidb.html

Proton binding sites and conformational analysis of H<SUP>+</SUP>K<SUP>+</SUP>-ATPase

It is proposed that the hydronium ion, H<SUB>3</SUB>O<SUP>+</SUP>, binds to the E1 conformation of the α-subunit of gastric proton pump. The H<SUB>3</SUB>O<SUP>+</SUP> binding cavities are characterized parametrically based on valence, sequence, geometry, and size considerations from comparative modeling. The cavities have scope for accommodating monovalent cations of different ionic radii. The H3O+ transport is proposed to be aided by arenes which are arranged regularly along the pump starting from N-domain through the transmembrane region. Step-by-step structural changes accompanying H<SUB>3</SUB>O<SUP>+</SUP> occlusion are studied in detail. The observations corroborate well with earlier experimental studies

Chemical Physics

A temperature-dependent effective potential explains CO binding to myoglobi

Some aspects of the algebraic description of anharmonic dynamics

A formally exact Lie-algebraic description of the dynamics on anharmonic potential energy surfaces is developed. The anharmonic hamiltonians belong to infinite dimensional Lie-algebras. Two ways of decomposing the algebras in the boson representation are presented. The evolution operator resulting from these two methods, which differ in the ordering of the boson operators, is shown to correspond to the time dependent generalizations of normal coupled cluster method (NCCM) and the extended coupled cluster method (ECCM). Relative merits of the two approaches are discussed. The NCCM formalism is applied to calculate the O→n vibrational transition probabilities of an exponentially perturbed harmonic oscillator modeling the collinear inelastic collision of He + H2 system. Good agreement with the basis set expansion approach is obtained with the Lie-algebraic approach showing a better convergence pattern