Entropy and Free Energy of a Mobile Loop Based on the Crystal Structures of the Free and Bound Proteins

A mobile loop changes its conformation from "open" (free enzyme) to "closed" upon ligand binding. The difference in the Helmholtz free energy, ΔF(loop) between these states sheds light on the mechanism of binding. With our "hypothetical scanning molecular dynamics" (HSMD-TI) method ΔF(loop) = F(free) - F(bound) where F(free) and F(bound) are calculated from two MD samples of the free and bound loop states; the contribution of water is obtained by a thermodynamic integration (TI) procedure. In previous work the free and bound loop structures were both attached to the same "template" which was "cut" from the crystal structure of the free protein. Our results for loop 287-290 of AcetylCholineEsterase agree with the experiment, ΔF(loop)~ -4 kcal/mol if the density of the TIP3P water molecules capping the loop is close to that of bulk water, i.e., N(water) = 140 - 180 waters in a sphere of a 18 ? radius. Here we calculate ΔF(loop) for the more realistic case, where two templates are "cut" from the crystal structures, 2dfp.pdb (bound) and 2ace.pdb (free), where N(water) = 40 - 160; this requires adding a computationally more demanding (second) TI procedure. While the results for N(water) ≤ 140 are computationally sound, ΔF(loop) is always positive (18 ± 2 kcal/mol for N(water) = 140). These (disagreeing) results are attributed to the large average B-factor, 41.6 of 2dfp (23.4 ?(2) for 2ace). While this conformational uncertainty is an inherent difficulty, the (unstable) results for N(water) = 160 suggest that it might be alleviated by applying different (initial) structural optimizations to each template.     

Conformational search of peptides and proteins: Monte Carlo minimization with an adaptive bias method applied to the heptapeptide deltorphin

The energy function of a protein consists of a tremendous number of minima. Locating the global energy minimum (GEM) structure, which corresponds approximately to the native structure, is a severe problem in global optimization. Recently we have proposed a conformational search technique based on the Monte Carlo minimization (MCM) method of Li and Scheraga, where trial dihedral angles are not selected at random within the range [-180 degrees,180 degrees ] (as with MCM) but with biased probabilities depending on the increased structure-energy correlations as the GEM is approached during the search. This method, called the Monte Carlo minimization with an adaptive bias (MCMAB), was applied initially to the pentapeptide Leu-enkephalin. Here we study its properties further by applying it to the larger peptide with bulky side chains, deltorphin (H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH(2)). We find that on average the number of energy minimizations required by MCMAB to locate the GEM for the first time is smaller by a factor of approximately three than the number required by MCM-in accord with results obtained for Leu-enkephalin.     

A computational foray into the formation and reactivity of metallabenzenes

Various metallabenzene complexes, analogues of benzene where one CH unit has been replaced by an organometallic fragment, have been reported in the literature. A detailed theoretical investigation on the chemistry of these complexes is presented here. This includes an evaluation of their aromaticity, the mechanisms of formation of osmium, iridium, and platinum metallabenzene complexes, and one intriguing aspect of their chemistry, the formation of cyclopentadienyl (Cp) complexes. X-ray photoelectron spectroscopy (XPS) measurements on two osmabenzene examples are also presented. In addition, diffuse functions for use with the SDD and SDB-cc-pVDZ basis set-RECP combinations are presented for the transition metals.     

Hybrid composites of monodisperse pi-conjugated rodlike organic compounds and semiconductor quantum particles

Composite materials of quantum particles (Q-particles) arranged in layers within crystalline powders of pi-conjugated, rodlike dicarboxylic acids are reported. The synthesis of the composites, either as three-dimensional crystals or as thin films at the air-water interface, comprises a two-step process: 1) The preparation of the Cd salts 6 (Cd), 8 (Cd) or Pb salts 6 (Pb), 8 (Pb) of the oligo(p-phenyleneethynylene)dicarboxylic acids 6 (H), 8 (H), in which the metal ions are arranged in ribbons and are separated by the long axis of the organic molecules, as demonstrated by X-ray powder diffraction analysis of the solids and grazing incidence X-ray diffraction analysis of the films on water. 2) Topotactic solid/gas reaction of these salts with H(2)S to convert the metal ions into Q-particles of CdS or PbS embedded in the organic matrix that consists of the acids 6 (H) and 8 (H). These hybrid materials have been characterized by X-ray photoelectron spectroscopy and transmission electron microscopy.     

Optimization of the GB/SA solvation model for predicting the structure of surface loops in proteins

Implicit solvation models are commonly optimized with respect to experimental data or Poisson-Boltzmann (PB) results obtained for small molecules, where the force field is sometimes not considered. In previous studies, we have developed an optimization procedure for cyclic peptides and surface loops in proteins based on the entire system studied and the specific force field used. Thus, the loop has been modeled by the simplified solvation function E(tot) = E(FF) (epsilon = 2r) + Sigma(i) sigma(i)A(i), where E(FF) (epsilon = nr) is the AMBER force field energy with a distance-dependent dielectric function, epsilon = nr, A(i) is the solvent accessible surface area of atom i, and sigma(i) is its atomic solvation parameter. During the optimization process, the loop is free to move while the protein template is held fixed in its X-ray structure. To improve on the results of this model, in the present work we apply our optimization procedure to the physically more rigorous solvation model, the generalized Born with surface area (GB/SA) (together with the all-atom AMBER force field) as suggested by Still and co-workers (J. Phys. Chem. A 1997, 101, 3005). The six parameters of the GB/SA model, namely, P(1)-P(5) and the surface area parameter, sigma (programmed in the TINKER package) are reoptimized for a "training" group of nine loops, and a best-fit set is defined from the individual sets of optimized parameters. The best-fit set and Still's original set of parameters (where Lys, Arg, His, Glu, and Asp are charged or neutralized) were applied to the training group as well as to a "test" group of seven loops, and the energy gaps and the corresponding RMSD values were calculated. These GB/SA results based on the three sets of parameters have been found to be comparable; surprisingly, however, they are somewhat inferior (e.g, of larger energy gaps) to those obtained previously from the simplified model described above. We discuss recent results for loops obtained by other solvation models and potential directions for future studies.     

Si-C-bound alkyl chains on oxide-free Si: towards versatile solution preparation of electronic transport quality monolayers

We show that electronic transport quality alkyl chain mono-layers can be prepared from dilute solution, rather than from neat alkanes, and on Si (100) instead of (111) surfaces. High monolayer quality was deduced from XPS and from comparing current-voltage curves of Hg/alkyl/Si junctions with those for junctions with monolayers made from neat alkanes. XPS shows that limited surface oxidation does not harm the integrity of the monolayer. Solution preparation significantly widens the range of molecules that can be used for transport studies.     

Acoustic centering of sources measured by surrounding spherical microphone arrays

The radiation patterns of acoustic sources have great significance in a wide range of applications, such as measuring the directivity of loudspeakers and investigating the radiation of musical instruments for auralization. Recently, surrounding spherical microphone arrays have been studied for sound field analysis, facilitating measurement of the pressure around a sphere and the computation of the spherical harmonics spectrum of the sound source. However, the sound radiation pattern may be affected by the location of the source inside the microphone array, which is an undesirable property when aiming to characterize source radiation in a unique manner. This paper presents a theoretical analysis of the spherical harmonics spectrum of spatially translated sources and defines four measures for the misalignment of the acoustic center of a radiating source. Optimization is used to promote optimal alignment based on the proposed measures and the errors caused by numerical and array-order limitations are investigated. This methodology is examined using both simulated and experimental data in order to investigate the performance and limitations of the different alignment methods.     

Realization of quantum walks with negligible decoherence in waveguide lattices

Quantum random walks are the quantum counterpart of classical random walks, and were recently studied in the context of quantum computation. Physical implementations of quantum walks have only been made in very small scale systems severely limited by decoherence. Here we show that the propagation of photons in waveguide lattices, which have been studied extensively in recent years, are essentially an implementation of quantum walks. Since waveguide lattices are easily constructed at large scales and display negligible decoherence, they can serve as an ideal and versatile experimental playground for the study of quantum walks and quantum algorithms. We experimentally observe quantum walks in large systems ( approximately 100 sites) and confirm quantum walks effects which were studied theoretically, including ballistic propagation, disorder, and boundary related effects.