Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations Board 16 Modelling of the Flexible Protein Histatin 5 16-POS

Poster Abstracts

Carolina Cragnell , Marie Skepö. Lund University, Lund, Sweden.

The existence of functional disordered (unstructured) proteins has been recognized for many years. However, due to the classical structure-function paradigm, the functional role of intrinsically disordered proteins has only recently been recognized. Biochemical evidence has since shown that these proteins are functional, and that the lack of a folded structure is related to their function. We would like to present results from a combined experimental and theoretical study, where the aim is to develop a model for flexible proteins and to relate the lack of structure of the proteins in solution with their function and structure when adsorbed to surfaces. For this purpose, we are combining atomistic and coarse-grained modelling, with simulation techniques such as molecular dynamics and Monte Carlo simulations. The simulations are compared with SAXS experiments of a model protein (Histatin 5). We will show simulated scattering curves that are in good agreement SAXS. At high salt concentration, Histatin 5 behaves as a neutral polymer, and at low salt concentration, a repulsive peak is obtained at low q. In the latter regime, it is the net charge of the protein that is of importance for the inter molecular interaction and not the charge distribution. Preliminary results also indicates that the peptide is more streched out in low pH solutions as well as in prescence of divalent ions such as Zn2+, Mg2+, and Ca2+, This indicate that electrostatic interactions indeed are important for Histatin 5 bulk structure.

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