Molecular flexibility controls a number of key processes ranging from protein folding to the design of advanced materials. However, the detailed understanding of its impact on a given process is poorly understood. Direct investigation of this phenomenon by experimental means, is a challenging endeavor, as the microscopic details are frequently hidden from macroscopic observations. Computational simulations, on the other hand, provide detailed information regarding molecular dynamics and flexibility. The theoretical approach is thus crucial in both understanding the experimental results and in expanding the underlying conceptual framework.

The present project proposes to utilize state-of-the-art computational techniques to address the importance of molecular flexibility across a range of carefully selected examples from the life sciences. The examples, which can be classified under the headings: (i) peptides and spectroscopy, (ii) protein structure and flexibility, and (iii) enzyme related transformations, have been chosen to span multiple time and length scales and thus to highlight the diverse and wide-reaching nature of molecular flexibility. The selected examples exhibit a significant degree of complementarity and synergy with one another and are all associated with their own applicative importance in different areas of (bio)chemistry.

In addition to the scientific research proposed, the project aims to consolidate a highly successful and competitive platform in computational life sciences that has been established at the RBI. This platform was already recognized through the granting of an EU-FP6 project (2007-2010). The current project team is thus well equipped for the proposed work and exhibits a good balance between senior researchers, with excellent track records, and junior scientists with outstanding potential. The support of the project team by HrZZ is crucial for maintaining their competitiveness in the international scientific community of computational life sciences.