Visualization: Multi-scale visualization of binding processes related to conformational changes of proteins for Alzheimer’s disease research

Conformational changes of proteins occur as effect of external stimuli and can lead to pathogenic states. E.g. proteins can aggregate into β sheet-rich fibrillar assemblies, known as amyloid fibrils, which cause Alzheimer’s disease. These proteins are studied using molecular imaging probes that attach themselves to the proteins and are visible in luminescence spectroscopies. A class of novel probes denoted luminescent conjugated polythiophenes (LCPs), proposed by P. Nilsson and coworkers at LiU, are conformationally flexible. This alters the LCP conformations enabling optical imaging. The optical properties of the probes are conformation dependent to a degree that makes it possible to distinguish probes that are attached to protein aggregates from those that are not. In this context, one- and two-photon excitation fluorescence and absorption spectroscopies are employed.

In the present project we will address the chromatic shifts that arise due to the surface interactions. The detailed microscopic understanding of how these flexible probes interact with amyloid proteins (and therefore also how their conformations change upon binding) is largely missing. We will address this point by a combination of molecular dynamics (MD) simulations and response theory QM/MM calculations in combination with visualization tools developed to more efficiently explore the vast number of degrees of freedom involved in the binding process.