Protein unfolding by interfaces and interactions between polycyclic aromatic hydrocarbons

Licentiate thesis, 2004

In order to theoretically study large and complex systems, a variety of approaches that can be categorized loosely as top-down or bottom-up are followed. While our vision is to bridge the gap between these approaches and use them together in multiscale materials modeling, the present thesis is limited to give examples of each type of approach in the study of soft-matter systems. In the first part of the thesis, a top-down approach to the study of interface-induced protein unfolding on hydrophobic and polar interfaces, respectively, is presented. We use a two-dimensional lattice model and an exhaustive enumeration search for the ground state structures for a set of model proteins of length 20 residues. A comparative model study of the effects of the two types of interfaces show them to induce similar behaviour, however, with stronger effects for hydrophobic interfaces. The unfolding is found to proceed by a large and sudden loss of native contacts. Further, the resistance of proteins to unfolding on hydrophobic interfaces is in our model positively correlated with (i) the magnitude of the folding energy in the native-state structure, (ii) the thermal stability or energy gap for that structure, and (iii) the interface energy for native-state adsorption. We find these factors to be of roughly equal importance. Finally, experiments that might test the predicted correlations are proposed. The second part of the thesis presents a bottom-up approach, a first-principles calculation on dimers of polycyclic aromatic hydrocarbon (PAH) molecules. In sparse matter, to which these and also proteins belong,the van der Waals forces, which are weak but long-ranged, have important effects. The PAHs consist of aromatic rings, molecular units that also appear in the side chains of amino acids. A recently developed van der Waals density functional [Phys.Rev.Lett. 91, 126402 (2003)] for planar geometry is used in an otherwise standard implementation of the density functional theory to calculate the van der Waals interactions between the PAH molecules. Calculated values for binding distances and energies of dimers of benzene, naphthalene, anthracene and pyrene are consistent with those of experiments and other theoretical studies. This pilot study gives promise for deepened investigations of interactions of proteins, mutually and at interfaces.