Intrinsically disordered proteins (IDPs) are an important kind of proteins able to perform a biological function without a well defined tertiary structure. The conformational disordered states may confer special properties to IDPs and make them the major players in a large number of pathologies . The most studied IDPs are amyloid β (Aβ) and Alpha Synuclein (αSyn) related, respectively, to Alzheimer's and Parkinson’s disease. These peptides are unfolded in the monomeric state, while as a result of β-aggregation processes originate amyloid fibrils, the main hallmarks of the corrisponding disease .
A suitable approach to study IDPs is to exploit suitable ensembles of disordered structures as determined, for example, by molecular dynamic simulations, and to estimate their relative population weights according data .
We have developed a new method able to describe the conformational disorder of IDPs on the basis of heterogeneous conformational ensembles generated by random sampling and on molecular dynamics simulations coupled with the principle of maximum entropy. This method is here applied to the analysis of Small Angle X-ray Scattering (SAXS) data.
We present the results of simulations performed to validate the method and its preliminary application to synchrotron SAXS data recorded on diluted water solutions of Aβ[1-40] and αSyn.
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