Intrinsically Disordered Energy Landscapes

This is the final version. It was first published by NPG at http://www.nature.com/srep/2015/150522/srep10386/full/srep10386.html?WT.ec_id=SREP-639%2C638-20150526#abstract.Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ?intrinsically disordered? landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.The authors thank Prof. Jane Clarke, Dr. Chris Whittleston, Dr. Joanne Carr, Dr. Iskra Staneva and Dr. David de Sancho for helpful discussions. Y.C. and A.J.B. acknowledge funding from the EPSRC grant number EP/I001352/1, D.C. gratefully acknowledges the Cambridge Commonwealth European and International Trust for financial support and D.J.W. the ERC for an Advanced Grant

Bow shock and upstream phenomena at Mars

Zakharov, 1992). Previous investigations of planetary bow shocks have established that their position, shape and jump conditions are functions of the upstream flow parameters and the nature of the solar wind – planet interaction (Spreiter and Stahara, 1980; Slavin et al., 1983; Russell, 1985). At Mars, however, the exact nature of the solar wind interaction was elusive due to the lack of low altitude plasma and magnetic field measurements (e.g., Axford, 1991). In fact our knowledge of the nature of the interaction of Mars with the solar wind was incomplete until the arrival of MGS and the acquisition of close-in magnetic field data (Acuña et al., 1998). As detailed by a series of review papers in this monograph, the Mars Global Surveyor (MGS) mission has now shown that the Mars environment is very complex with strong, highly structured crustal magnetic remnants in the southern hemisphere, while the northern hemisphere experiences the direct impingement of solar wind plasma. This review paper first presents a survey of the observations on the Martian bow shock and the upstream phenomena in the light of results from all the missions to date. It also discusses the kinetic properties of the Martian bow shock compared to the predictions of simulations studies. Then i