Rough interfaces, accurate predictions: The necessity of capillary modes in a minimal model of nanoscale hydrophobic solvation

Modern theories of the hydrophobic effect highlight its dependence on length scale, emphasizing in particular the importance of interfaces that emerge in the vicinity of sizable hydrophobes. We recently showed that a faithful treatment of such nanoscale interfaces requires careful attention to the statistics of capillary waves, with significant quantitative implications for the calculation of solvation thermodynamics. Here we show that a coarse-grained lattice model in the spirit of those pioneered by Chandler and coworkers, when informed by this understanding, can capture a broad range of hydrophobic behaviors with striking accuracy. Specifically, we calculate probability distributions for microscopic density fluctuations that agree very well with results of atomistic simulations, even many standard deviations from the mean, and even for probe volumes in highly heterogeneous environments. This accuracy is achieved without adjustment of free parameters, as the model is fully specified by well-known properties of liquid water. As illustrative examples of its utility, we characterize the free energy profile for a solute crossing the air-water interface, and compute the thermodynamic cost of evacuating the space between extended nanoscale surfaces. Together, these calculations suggest that a highly reduced model for aqueous solvation can serve as the basis for efficient multiscale modeling of spatial organization driven by hydrophobic and interfacial forces.Comment: 14 pages, 7 figure

Efforts Towards the Total Synthesis of Labelled CCL2 Proteins and Dipeptide Chemotaxis Inhibitors

Chemokines such as CCL2 are small proteins with molecular weights between 8-10 kDa. They promote chemotaxis and play a vital role in the recruitment of leukocytes to the site of inflammation. Given their key biological functions, understanding their mechanism of action and inhibiting their action has therapeutic potential in a range of diseases. Selective inhibitors of CCL2 induced chemotaxis based on the diketopiperazine (DKP) natural product, cyclo(13,15-dichloro-L-Pro-L-Tyr) were recently reported by the Cobb group. In order to develop this work further and to produce an expanded library, we optimised an on-resin DKP synthesis. In collaboration with researchers at Newcastle Medical School, chemotaxis assays were performed in an attempted to define the structural features (required for inhibition) of the DKPs. To faciliate the aforementioned work, facile synthetic routes to a number of novel heteraromatic and proline derivatives were developed. The posttranslational nitration of CCL2 is used as a mechanism to a modulate CCL2. However, in all previous studies nitrated CCL2 was utilised as a heterogeneous mix of protein. Having access to single site nitrated CCL2 will enable the mechanism of abrogration to be pinpointed to a specific residue. Therefore, the total chemical synthesis of both native CCL2 and site-specifically nitrated CCL2 via solid phase peptide synthesis (SPPS) was undertaken. The work focused on the potential application of microwave assisted SPPS as a means to rapidly access the target proteins

Bribery and Identity:Evidence from Sudan

Using a unique dataset we examine the determinants of social identification in Sudan. We find that social identification is high, with little evidence that such identities compete with one another. Poorer people tend to have greater social identification and tribal identification declines with the level of education, as does identity with religion and the Arab world. We also find that being asked for a bribe is associated with significantly lower levels of social identification, particularly those linked with the tribe, the state (i.e. a region) and the nation. Finally we analyse the probability of being asked for a bribe

Bribery and Identity:Evidence from Sudan

Using a unique dataset we examine the determinants of social identification in Sudan. We find that social identification is high, with little evidence that such identities compete with one another. Poorer people tend to have greater social identification and tribal identification declines with the level of education, as does identity with religion and the Arab world. We also find that being asked for a bribe is associated with significantly lower levels of social identification, particularly those linked with the tribe, the state (i.e. a region) and the nation. Finally we analyse the probability of being asked for a bribe