MATHEON Project A19: Modelling and Optimization

of Functional Molecules

In recent years we have been successful in advancing so-called conformation dynamics algorithms (with a widespread portfolio of applications such as conformation changes of oligopeptides, protein folding, DNA flexibility, ligand design, etc.) including the corresponding mathematical modelling and simulation issues (see Project “Markov State Models: Theory and Algorithms”), and the incorporation of experimental data into the modelling and simulation context (see project “From single molecule experiments to models of  molecular kinetics”). Next we will pursue the technological goal of design and optimization of functional molecules. The focus in this still quite large target field will be on molecular sensors (biocomputing group) and on enzyme design (our cooperation partner ZIB).

Selected Publications

  • Haack, F. and Röblitz, S. and Scharkoi, O. and Schmidt, B. and Weber, M. (2010) Adaptive spectral clustering for conformation analysis. In: ICNAAM 2010: International Conference of Numerical Analysis and Applied Mathematics. AIP Conf. Proc. (1281). AIP, pp. 1585-1588.


  • Sarich, M. and Noe, F. and Schütte, Ch. (2010) On the Approximation Quality of Markov State Models. Multiscale Model. Simul., 8 (4). pp. 1154-1177.


  • Noe, F. and Schütte, Ch. and Vanden-Eijnden, E. and Reich, L. and Weikl, T. (2009) Constructing the Full Ensemble of Folding Pathways from Short Off-Equilibrium Simulations. Proc. Natl. Acad. Sci. USA, 106 (45). pp. 19011-19016.


  • N. Djurdjevac, M. Sarich, and Ch. Schütte. On Markov state models for metastable processes.Proceeding of the ICM 2010, special issue “Invited lectures”, 2010.

  • Sarich, M. and Schütte, Ch. (2011) Approximating Selected Non-dominant Timescales by Markov State Models. CPAM (Submitted)

  • Prinz, J.-H. and Wu, H. and Sarich, M. and Keller, B. and Fischbach, M. and Held, M. and Chodera, J. D. and Schütte, Ch. and Noé, F. (2011) Markov models of molecular kinetics: Generation and Validation. J. Chem. Phys. , 134 . p. 174105.

  • Schütte, Ch. and Noé, F. and Lu, Jianfeng and Sarich, M. and Vanden-Eijnden, E. (2011) Markov State Models Based on Milestoning. J. Chem. Phys. 134 (20). 204105 .


Christof Schuette, Frank Noe,

Peter Deuflhard

Project researchers

Marco Sarich, Burkhard Schmidt, Frank Noe,
Marcus Weber, Christof Schuette, Peter Deuflhard, Tim Conrad



P. Deuflhard (ZIB), E. Vanden Eijnden (Courant, NYU), M. Dellnitz (U Paderborn), V. Pande (Stanford)