Estimating Translational and Orientational Entropies Using the k-Nearest Neighbors Algorithm.

Inhomogeneous fluid solvation theory (IFST) and free energy perturbation (FEP) calculations were performed for a set of 20 solutes to compute the hydration free energies. We identify the weakness of histogram methods in computing the IFST hydration entropy by showing that previously employed histogram methods overestimate the translational and orientational entropies and thus underestimate their contribution to the free energy by a significant amount. Conversely, we demonstrate the accuracy of the k-nearest neighbors (KNN) algorithm in computing these translational and orientational entropies. Implementing the KNN algorithm within the IFST framework produces a powerful method that can be used to calculate free-energy changes for large perturbations. We introduce a new KNN approach to compute the total solute-water entropy with six degrees of freedom, as well as the translational and orientational contributions. However, results suggest that both the solute-water and water-water entropy terms are significant and must be included. When they are combined, the IFST and FEP hydration free energies are highly correlated, with an R(2) of 0.999 and a mean unsigned difference of 0.9 kcal/mol. IFST predictions are also highly correlated with experimental hydration free energies, with an R(2) of 0.997 and a mean unsigned error of 1.2 kcal/mol. In summary, the KNN algorithm is shown to yield accurate estimates of the combined translational-orientational entropy and the novel approach of combining distance metrics that is developed here could be extended to provide a powerful method for entropy estimation in numerous contexts.This work was supported by the MRC under grant ML/L007266/1. All calculations were performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/) provided by Dell Inc. using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and were funded by the EPSRC under grants EP/F032773/1 and EP/J017639/1.This is the final published version. It's also available from the journal website can be found at: http://pubs.acs.org/doi/abs/10.1021/ct500415

Nonlinear Autoregressive Models and Long Memory

This note shows that regime switching nonlinear autoregressive models widely used in the time series literature can exhibit arbitrary degrees of long memory via appropriate definition of the model regimes.Long memory, Nonlinearity

Is it possible to discriminate between different switching regressions models? An empirical investigation

In this paper we study, using the sup LR test, the possibility of discrimination between two classes of models: the Markov switching models of Hamilton (1989) and the Threshold Auto-Regressive Models (TAR) of Lim and Tong (1980). This work is motivated by the fact that generally practicians use, in applications, switching models without any statistical justification. Using experiment simulations, we show that it is very difficult to discriminate between the MSAR and the SETAR models specially using large samples. This means that when the null hypothesis is rejected, it appears that different switching models are significant. Moreover, the results show that the power of the sup LR test is sensitive to the mean, the noise variance and the delay parameter. Then, we apply this methodology to two time series: the US GNP growth rate and the US/UK exchange rate. We shall retain retain a Markov switching process for the US GNP growth rate and the US/UK exchange rate (monthly data). For the US/UK exchange rate (quarterly data), we accept the null hypothesis of a random walk.Switching Models, Sup LR test, Empirical power, Exchange rate

The cleanability of stainless steel used as a food contact surface: an updated short review

The effect of surface roughness on the cleanability of stainless steel as used in the foodindustry

A Large Scale Study of Hydration Environments Through Hydration Sites

Hydration sites are locations of interest to water and they can be used to classify the behaviour of water around chemical motifs commonly found on the surface of proteins. Inhomogeneous fluid solvation theory (IFST) is a method for calculating hydration free energy changes from molecular dynamics (MD) trajectories. In this paper hydration sites are identified from MD simulations of 380 diverse protein structures. The hydration free energies of the hydration sites are calculated using IFST and distributions of these free energy changes are analysed. The results show that for some hydration sites near features conventionally regarded as attractive to water, such as hydrogen bond donors, the water molecules are actually relatively weakly bound and are easily displaced. We also construct plots of the spatial density of hydration sites with high medium and low hydration free energy changes which represent weakly and strongly bound hydration sites. It is found that these plots show consistent features around common polar amino acids for all of the proteins studied

Quantifying the entropy of binding for water molecules in protein cavities by computing correlations.

Protein structural analysis demonstrates that water molecules are commonly found in the internal cavities of proteins. Analysis of experimental data on the entropies of inorganic crystals suggests that the entropic cost of transferring such a water molecule to a protein cavity will not typically be greater than 7.0 cal/mol/K per water molecule, corresponding to a contribution of approximately +2.0 kcal/mol to the free energy. In this study, we employ the statistical mechanical method of inhomogeneous fluid solvation theory to quantify the enthalpic and entropic contributions of individual water molecules in 19 protein cavities across five different proteins. We utilize information theory to develop a rigorous estimate of the total two-particle entropy, yielding a complete framework to calculate hydration free energies. We show that predictions from inhomogeneous fluid solvation theory are in excellent agreement with predictions from free energy perturbation (FEP) and that these predictions are consistent with experimental estimates. However, the results suggest that water molecules in protein cavities containing charged residues may be subject to entropy changes that contribute more than +2.0 kcal/mol to the free energy. In all cases, these unfavorable entropy changes are predicted to be dominated by highly favorable enthalpy changes. These findings are relevant to the study of bridging water molecules at protein-protein interfaces as well as in complexes with cognate ligands and small-molecule inhibitors.Acknowledgments go to the Cambridge High Performance Computing Service for technical assistance, Professor Mike Gilson for helpful discussions, and Professor Bruce Tidor for support. This work was supported by the MRC under grant ML/L007266/1. All calculations were performed using the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/) provided by Dell, Inc., using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England and were funded by the EPSRC under grants EP/F032773/1 and EP/J017639/1.This is the final published version. It first appeared in Biophysics Journal, Volume 108 February 2015, 928–936 DOI: http://dx.doi.org/10.1016/j.bpj.2014.12.035

T violation in (Lambda_b -> Lambda l^+ l^-) decay beyond standard model

Using the most general, model independent form of effective Hamiltonian, the transverse polarization P_T of Lambda in Lambda_b -> Lambda l^+ l^- decay is studied. It is observed that the averaged is very sensitive to the existence of new physics and can attain large values, which can be measured at future colliders.Comment: 12 pages, 7 figures, LaTeX formatte

Inquiry into local safeguarding children boards in Wales

"The Committee agreed to conduct an inquiry into Local Safeguarding Children Boards to ensure that relevant organisations in each local authority area co-operate to safeguard and promote the welfare of children." - Page 9

Modulate your immune response using cereals

Institute of Food Science and Technology (IFST) Young Scientist Competition (2018