pH-dependent Peptide Aggregation through Multiscale Simulations
In physiological conditions proteins play a key role in many aspects of life. However, some processes like aggregation perturb the conditions making proteins lose their characteristic 3-dimensional shape and, therefore, their functionality. Protein aggregation are linked to major diseases (like Alzheimer or Huntington) and occur due to the change in the environmental conditions (such as temperature, concentration or pH).
In the field of numerical simulation there are standard methodologies to study temperature and concentration, but the treatment of the pH remains more elusive, because proteins present multiple sites that can bind or release protons and often they are coupled to each another. In this project we attempt to describe this latter aspect through multiscale modeling and simulation, connecting full-atom to single-bead coarse grained descriptions. Specifically, we are developing in-house pH-dependent algorithms, combining full-atom and coarse-grained descriptions. Our coarse-grained model is based on four types of amino acids (polar, hydrophobic and positively and negatively charged) and its physics is described by the most relevant interactions in protein systems, that is hydrogen bonds, hydrophobic and electrostatic interactions.
Postdoc: Marta Enciso
Collaboration with Christof Schuette
References:
M.Enciso, C.Schuette and L.Delle Site:"pH-dependent coarse-grained model of peptides", Soft Matter 9, 6118 (2013)
M.Enciso, C.Schuette and L.Delle Site:"pH-dependent Response of Coiled Coils: A Coarse-Grained Molecular Simulation Study", Molecular Physics, 111, 3363-3371 (2013); arXiv:1304.7241
M.Enciso, C.Schuette and L.Delle Site:"Influence of pH and sequence in peptide aggregation via molecular simulation"J.Chem.Phys.143, 243130 (2015)
Multiscale Modeling and Simulation of Ionic Liquid
For theoreticians, ionic liquids represent a major challenge. This is due to the fact
that intermolecular interactions are particularly strong because of ionic liquids'
ionicity. This, in turn, causes a subtle interplay between different scales which
is encoded in the measured macro- and mesoscopic properties and also in the
molecular electrostatic characteristics.
Therefore, force fields have to describe
the microscopic processes correctly in order to reproduce macroscopic properties
accurately over a large range of state variables. Herein, imidazolium-based
ionic liquids were studied at different scales, going from the detailed quantum
electronic scale to the classical atomistic scale. It is indicated how the information
gained at each level could be used for the other scales.
PhD Student (terminated project): Katharina Wendler
Collaboration with C.Holm, R.Berger and B.Kirchner
Selected References:
K.Wendler,M.Brehm, F.Malberg, B.Kirchner and L.Delle Site:
Journal of Chemical Theory & Computation, 8, 1570 (2012)
K.Wendler, F.Dommert, Y.Y.Zhao, R.Berger, C.Holm and L.Delle Site:
Faraday Discussions 154 (1), 111-132 (2012)
K.Wendler, S.Zahn, F.Dommert, R.Berger, C.Holm, B.Kirchner and L.Delle Site:
Journal of Chemical Theory & Computation,7, 2681 (2011)
Proton Wires via Water Chains on Metallic Surfaces
Metallic surfaces, due to their hydrophilicity, present fascinating possibilities to induce ordered two- and one-dimensional water networks stabilized by the adsorption interaction of water molecules onto the surface. Such networks may provide channels through which protons can move along paths of hydrogen bonds.
By ab initio studies of the proton transfer along water wires adsorbed on several different stepped metallic surfaces we have found that indeed one may have a thermally induced proton current along the water chain. However, most importantly, the process of proton hopping along the water chain may be the result of a more general property that is the capability of (some) water chains to promote autocatalytic and cooperatively-stabilized dissociation of water.
Collaboration with D.Donadio and L.M.Ghiringhelli
Selected References:
R.Scipioni, D.Donadio, L.M.Ghiringhelli and L.Delle Site:
Journal of Chemical Theory & Computation, 7, 2681 (2011)
D.Donadio, L.M.Ghiringhelli and L.Delle Site:
Journal of the American Chemical Society, 134, 19217 (2012); DOI: 10.1021/ja308899g
