Phonon-assisted absorption of hypersound in a rectangular quantum wire

The mechanisms of the Landau-Rumer process and of the process of two-phonon decay of microwave phonons are considered for a rectangular quantum wire. For GaAs wires with a free surface and various transverse dimensions, the coefficients of absorption of confined microwave phonons of the lowest hybrid width mode are calculated. The phononic and electronic mechanisms of hypersound absorption in rectangular wires and unbounded solids are compared. At low temperatures, the inclusion of cubic anharmonicity in a wire leads to an exponential temperature dependence of the hypersound absorption for the Landau-Rumer process and to the dominant absorption due to decay processes; in the latter case, the exponent of the frequency dependence decreases. At sufficiently high temperatures, the phonon-assisted absorption dominates over the electron-assisted absorption in a quantum wire of a nondegenerate material.     

New and fast statistical-thermodynamic method for computation of protein-ligand binding entropy substantially improves docking accuracy

We present a novel method to estimate the contributions of translational and rotational entropy to protein-ligand binding affinity. The method is based on estimates of the configurational integral through the sizes of clusters obtained from multiple docking positions. Cluster sizes are defined as the intervals of variation of center of ligand mass and Euler angles in the cluster. Then we suggest a method to consider the entropy of torsional motions. We validate the suggested methods on a set of 135 PDB protein-ligand complexes by comparing the averaged root-mean square deviations (RMSD) of the top-scored ligand docked positions, accounting and not accounting for entropy contributions, relative to the experimentally determined positions. We demonstrate that the method increases docking accuracy by 10-21% when used in conjunction with the AutoDock docking program, thus reducing the percent of incorrectly docked ligands by 1.4-fold to four-fold, so that in some cases the percent of ligands correctly docked to within an RMSD of 2 A is above 90%. We show that the suggested method to account for entropy of relative motions is identical to the method based on the Monte Carlo integration over intervals of variation of center of ligand mass and Euler angles in the cluster.     

Role of binding entropy in the refinement of protein-ligand docking predictions: analysis based on the use of 11 scoring functions

We present results of testing the ability of eleven popular scoring functions to predict native docked positions using a recently developed method (Ruvinsky and Kozintsev, J Comput Chem 2005, 26, 1089) for estimation the entropy contributions of relative motions to protein-ligand binding affinity. The method is based on the integration of the configurational integral over clusters obtained from multiple docked positions. We use a test set of 100 PDB protein-ligand complexes and ensembles of 101 docked positions generated by (Wang et al. J Med Chem 2003, 46, 2287) for each ligand in the test set. To test the suggested method we compared the averaged root-mean square deviations (RMSD) of the top-scored ligand docked positions, accounting and not accounting for entropy contributions, relative to the experimentally determined positions. We demonstrate that the method increases docking accuracy by 10-21% when used in conjunction with the AutoDock scoring function, by 2-25% with G-Score, by 7-41% with D-Score, by 0-8% with LigScore, by 1-6% with PLP, by 0-12% with LUDI, by 2-8% with F-Score, by 7-29% with ChemScore, by 0-9% with X-Score, by 2-19% with PMF, and by 1-7% with DrugScore. We also compared the performance of the suggested method with the method based on ranking by cluster occupancy only. We analyze how the choice of a clustering-RMSD and a low bound of dense clusters impacts on docking accuracy of the scoring methods. We derive optimal intervals of the clustering-RMSD for 11 scoring functions.     

Calculations of protein-ligand binding entropy of relative and overall molecular motions

In the context of virtual database screening, calculations of protein-ligand binding entropy of relative and overall molecular motions are challenging, owing to the inherent structural complexity of the ligand binding well in the energy landscape of protein-ligand interactions and computing time limitations. We describe a fast statistical thermodynamic method for estimation the binding entropy to address the challenges. The method is based on the integration of the configurational integral over clusters obtained from multiple docked positions. We apply the method in conjunction with 11 popular scoring functions (AutoDock, ChemScore, DrugScore, D-Score, F-Score, G-Score, LigScore, LUDI, PLP, PMF, X-Score) to evaluate the binding entropy of 100 protein-ligand complexes. The averaged values of binding entropy contribution vary from 6.2 to 9.1 kcal/mol, showing good agreement with literature. We calculate positional sizes and the angular volume of the native ligand wells. The averaged geometric mean of positional sizes in principal directions varies from 0.8 to 1.4 A. The calculated range of angular volumes is 3.3-11.8 rad(2). Then we demonstrate that the averaged six-dimensional volume of the native well is larger than the volume of the most populated non-native well in energy landscapes described by all of 11 scoring functions.     

The Structure of the BfrB-Bfd Complex Reveals Protein-Protein Interactions Enabling Iron Release from Bacterioferritin

Ferritin-like molecules are unique to cellular iron homeostasis because they can store iron at concentrations much higher than those dictated by the solubility of Fe(3+). Very little is known about the protein interactions that deliver iron for storage or promote the mobilization of stored iron from ferritin-like molecules. Here, we report the X-ray crystal structure of Pseudomonas aeruginosa bacterioferritin (Pa-BfrB) in complex with bacterioferritin-associated ferredoxin (Pa-Bfd) at 2.0 ? resolution. As the first example of a ferritin-like molecule in complex with a cognate partner, the structure provides unprecedented insight into the complementary interface that enables the [2Fe-2S] cluster of Pa-Bfd to promote heme-mediated electron transfer through the BfrB protein dielectric (～18 ?), a process that is necessary to reduce the core ferric mineral and facilitate mobilization of Fe(2+). The Pa-BfrB-Bfd complex also revealed the first structure of a Bfd, thus providing a first view to what appears to be a versatile metal binding domain ubiquitous to the large Fer2_BFD family of proteins and enzymes with diverse functions. Residues at the Pa-BfrB-Bfd interface are highly conserved in Bfr and Bfd sequences from a number of pathogenic bacteria, suggesting that the specific recognition between Pa-BfrB and Pa-Bfd is of widespread significance to the understanding of bacterial iron homeostasis.     

Sequence composition and environment effects on residue fluctuations in protein structures

Structure fluctuations in proteins affect a broad range of cell phenomena, including stability of proteins and their fragments, allosteric transitions, and energy transfer. This study presents a statistical-thermodynamic analysis of relationship between the sequence composition and the distribution of residue fluctuations in protein-protein complexes. A one-node-per-residue elastic network model accounting for the nonhomogeneous protein mass distribution and the interatomic interactions through the renormalized inter-residue potential is developed. Two factors, a protein mass distribution and a residue environment, were found to determine the scale of residue fluctuations. Surface residues undergo larger fluctuations than core residues in agreement with experimental observations. Ranking residues over the normalized scale of fluctuations yields a distinct classification of amino acids into three groups: (i) highly fluctuating-Gly, Ala, Ser, Pro, and Asp, (ii) moderately fluctuating-Thr, Asn, Gln, Lys, Glu, Arg, Val, and Cys, and (iii) weakly fluctuating-Ile, Leu, Met, Phe, Tyr, Trp, and His. The structural instability in proteins possibly relates to the high content of the highly fluctuating residues and a deficiency of the weakly fluctuating residues in irregular secondary structure elements (loops), chameleon sequences, and disordered proteins. Strong correlation between residue fluctuations and the sequence composition of protein loops supports this hypothesis. Comparing fluctuations of binding site residues (interface residues) with other surface residues shows that, on average, the interface is more rigid than the rest of the protein surface and Gly, Ala, Ser, Cys, Leu, and Trp have a propensity to form more stable docking patches on the interface. The findings have broad implications for understanding mechanisms of protein association and stability of protein structures.     

On the enhanced electrocatalytic activity of Pd overlayers on carbon-supported gold particles in hydrogen electrooxidation

Palladium-gold particles with varied composition were prepared by Pd electrochemical deposition on Au nanoparticles immobilized on model carbon support. Pd-Au/C catalysts were characterized ex situ by transmission electron microscopy, energy dispersive X-ray analysis and X-ray photoelectron spectroscopy, and in situ, by underpotential deposition of hydrogen and copper adatoms, and CO stripping. Hydrogen oxidation reaction on pristine and CO-poisoned Pd-Au/C particles was studied using rotating disk electrode (RDE) technique. It was found that the decrease of the effective Pd overlayer thickness below ca. two monolayers resulted in a two-fold increase of the exchange current density of the hydrogen oxidation reaction and in significant increase of CO tolerance.