Ulrich H.E. Hansmann
COMPUTATIONAL BIOPHYSICAL CHEMISTRY
Aggregation of Ab peptides
Free energy surfaces of GA and GB as folding progresses
Rational drug design or the pathology of various diseases such as cancer or Alzheimer’s require an understanding of the workings of cells on a molecular level. However, despite the remarkable progress in experimental machinery and techniques for producing and characterizing proteins, a detailed understanding of fundamental processes of protein folding, aggregation and interaction in a cell is still missing. Simulations can complement experiments and trace these processes, but unfortunately the numerical difficulties grow exponentially with the size of the system. This is because the complex form of the forces within and between proteins leads to a rough energy landscape with a large number of local minima acting as traps. Our lab develops algorithms and software to overcome this bottleneck and enable efficient simulations of large biomolecules. Examples are generalized-ensemble sampling and replica exchange techniques and our software package SMMP. We use these techniques developed in our lab to probe the mechanism of folding in selected small proteins and the conditions by which proteins mis-fold and aggregate. The later processes are often related to the outbreak of neurological and other diseases, and choice of the systems that we study is often motivated by their medical or pharmaceutical relevance. Protein-ligand binding and protein interaction networks belong to the same research direction and provide an interface for collaborations.
protein folding; aggregation; enhanced sampling techniques