Protein Structure & Function

Background and Motivation

Proteins are the workhorses of molecular life. They are a special type of biopolymer, and their synthesis and turnover is one of the major tasks performed in every cell. Proteins can function as catalysts of chemical reactions or as scaffolds in complex assemblies to name two prominent examples. Aberrant protein function, caused for example by errors in how the protein is synthesized, can be pathogenic. Prominent human diseases like cancer, Alzheimer's disease, or autoimmune diseases are linked to malfunctioning proteins. Proteins are complex systems, and, as nanoscale objects, they are subject to thermal fluctuations in their three-dimensional conformations. It is thus difficult to rationalize and predict how proteins respond and adapt to changes in environmental conditions or to possible interaction partners. A large number of proteins adopts well-defined and unique structures determined by their sequences while others, so-called intrinsically disordered proteins do not.

Our Approach

We use computer simulations to try to shed light on physicochemical processes underlying the folding and function of proteins. With regards to function, we focus primarily on the binding of molecular interaction partners from small molecules via peptides to other proteins. The most fundamental theoretical model is to describe the temporal evolution of the particles that constitute all matter (biological or not). Molecular dynamics is a manifestation of this type of model aided by approximations, which, for example, prohibit chemical reactions from proceeding. Over the years we have investigated protein folding (e.g., Beta3S), peptide aggregation (e.g., Amyloid β peptide), peptide binding (e.g. histone tails to bromodomains), and other topics using molecular dynamics.