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

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

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. &quot;Protein collapse&quot;, 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..

Characterization of calcium and magnesium binding domains of human 5-lipoxygenase

Two calcium binding sites, separated by about 9.3 Å, present in the loops that connect the β-sheets of N-terminal domain contain the ligating residues F14, A15, G16, D79, and D18, D19, L76, respectively. Magnesium is found to bind in regions, which are marginally different owing to the disparity in the ionic radii of Ca<SUP>2+</SUP> and Mg<SUP>2+</SUP>. The entropy analysis on the loops of 5-lipoxygenase, implementing the wormlike chain model, explains that the N-terminal β-barrel is well suited to accommodate calcium binding sites. The large buried side chain area of W102 (compared to W13 and W75) and comparatively smaller fraction of side chain exposed to polar atoms corroborate the calcium induced higher affinity to phosphatidylcholine (PC). However, W80 lying in close proximity of the calcium binding sites is expected to have considerable PC affinity but negligible calcium induced effect on PC binding

Chemical Physics

A temperature-dependent effective potential explains CO binding to myoglobi

Cation-aromatic database

Cation–aromatic database (CAD) is a publicly available web-based database that aims to provide further understanding of interaction between a cation and the π interactions. A tool to identify the interactions in a user-given protein is also added to the database

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

The time-dependent coupled cluster approach to molecular photodissociation dynamics

The time-dependent coupled cluster method (TDCCM) has been applied to the photodissociation dynamics of linear triatomics using the Beswick-Jortner model. The autocorrelation function and absorption spectra have been evaluated and the convergence of the method has been tested by evaluating the autocorrelation function at different truncations of the S-matrix elements. It is found that the TDCCM approach converges to exact results quite quickly