@article{KlusBittracherSchusteretal.2018, author = {Klus, Stefan and Bittracher, Andreas and Schuster, Ingmar and Sch{\"u}tte, Christof}, title = {A kernel-based approach to molecular conformation analysis}, volume = {149}, journal = {Journal of Chemical Physics}, number = {24}, doi = {10.1063/1.5063533}, year = {2018}, abstract = {We present a novel machine learning approach to understanding conformation dynamics of biomolecules. The approach combines kernel-based techniques that are popular in the machine learning community with transfer operator theory for analyzing dynamical systems in order to identify conformation dynamics based on molecular dynamics simulation data. We show that many of the prominent methods like Markov State Models, EDMD, and TICA can be regarded as special cases of this approach and that new efficient algorithms can be constructed based on this derivation. The results of these new powerful methods will be illustrated with several examples, in particular the alanine dipeptide and the protein NTL9.}, language = {en} } @article{ZhangSchuette2017, author = {Zhang, Wei and Sch{\"u}tte, Christof}, title = {Reliable approximation of long relaxation timescales in molecular dynamics}, volume = {19}, journal = {Entropy}, number = {7}, doi = {10.3390/e19070367}, year = {2017}, language = {en} } @article{HartmannRichterSchuetteetal.2017, author = {Hartmann, Carsten and Richter, Lorenz and Sch{\"u}tte, Christof and Zhang, Wei}, title = {Variational characterization of free energy: theory and algorithms}, volume = {19}, journal = {Entropy}, number = {11}, doi = {10.3390/e19110626}, pages = {626}, year = {2017}, language = {en} } @article{SchulzYamamotoKlosseketal.2019, author = {Schulz, Robert and Yamamoto, Kenji and Klossek, Andr{\´e} and Rancan, Fiorenza and Vogt, Annika and Sch{\"u}tte, Christof and R{\"u}hl, Eckart and Netz, Roland R.}, title = {Modeling of Drug Diffusion Based on Concentration Profiles in Healthy and Damaged Human Skin}, volume = {117}, journal = {Biophysical Journal}, number = {5}, doi = {10.1016/j.bpj.2019.07.027}, pages = {998 -- 1008}, year = {2019}, abstract = {Based on experimental drug concentration profiles in healthy as well as tape-stripped ex vivo human skin, we model the penetration of the antiinflammatory drug dexamethasone into the skin layers by the one-dimensional generalized diffusion equation. We estimate the position-dependent free-energy and diffusivity profiles by solving the conjugated minimization problem, in which the only inputs are concentration profiles of dexamethasone in skin at three consecutive penetration times. The resulting free-energy profiles for damaged and healthy skin show only minor differences. In contrast, the drug diffusivity in the first 10 μm of the upper skin layer of damaged skin is 200-fold increased compared to healthy skin, which reflects the corrupted barrier function of tape-stripped skin. For the case of healthy skin, we examine the robustness of our method by analyzing the behavior of the extracted skin parameters when the number of input and output parameters are reduced. We also discuss techniques for the regularization of our parameter extraction method.}, language = {en} } @article{BittracherKoltaiKlusetal.2018, author = {Bittracher, Andreas and Koltai, P{\´e}ter and Klus, Stefan and Banisch, Ralf and Dellnitz, Michael and Sch{\"u}tte, Christof}, title = {Transition manifolds of complex metastable systems: Theory and data-driven computation of effective dynamics}, volume = {28}, journal = {Jounal of Nonlinear Science}, number = {2}, doi = {10.1007/s00332-017-9415-0}, pages = {471 -- 512}, year = {2018}, abstract = {We consider complex dynamical systems showing metastable behavior but no local separation of fast and slow time scales. The article raises the question of whether such systems exhibit a low-dimensional manifold supporting its effective dynamics. For answering this question, we aim at finding nonlinear coordinates, called reaction coordinates, such that the projection of the dynamics onto these coordinates preserves the dominant time scales of the dynamics. We show that, based on a specific reducibility property, the existence of good low-dimensional reaction coordinates preserving the dominant time scales is guaranteed. Based on this theoretical framework, we develop and test a novel numerical approach for computing good reaction coordinates. The proposed algorithmic approach is fully local and thus not prone to the curse of dimension with respect to the state space of the dynamics. Hence, it is a promising method for data-based model reduction of complex dynamical systems such as molecular dynamics.}, language = {en} } @article{HartmannJoesterSchuetteetal.2026, author = {Hartmann, Carsten and J{\"o}ster, Annika and Sch{\"u}tte, Christof and Sikorski, Alexander and Weber, Marcus}, title = {Importance sampling of unbounded random stopping times: computing committor functions and exit rates without reweighting}, arxiv = {http://arxiv.org/abs/2601.01489}, year = {2026}, abstract = {Rare events in molecular dynamics are often related to noise-induced transitions between different macroscopic states (e.g., in protein folding). A common feature of these rare transitions is that they happen on timescales that are on average exponentially long compared to the characteristic timescale of the system, with waiting time distributions that have (sub)exponential tails and infinite support. As a result, sampling such rare events can lead to trajectories that can be become arbitrarily long, with not too low probability, which makes the reweighting of such trajectories a real challenge. Here, we discuss rare event simulation by importance sampling from a variational perspective, with a focus on applications in molecular dynamics, in particular the computation of committor functions. The idea is to design importance sampling schemes that (a) reduce the variance of a rare event estimator while controlling the average length of the trajectories and (b) that do not require the reweighting of possibly very long trajectories. In doing so, we study different stochastic control formulations for committor and mean first exit times, which we compare both from a theoretical and a computational point of view, including numerical studies of some benchmark examples.}, language = {en} } @misc{EncisoSchuetteDelleSite2015, author = {Enciso, Marta and Sch{\"u}tte, Christof and Delle Site, Luigi}, title = {Influence of pH and sequence in peptide aggregation via molecular simulation}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-55805}, year = {2015}, abstract = {We employ a recently developed coarse-grained model for peptides and proteins where the effect of pH is automatically included. We explore the effect of pH in the aggregation process of the amyloidogenic peptide KTVIIE and two related sequences, using three different pH environments. Simulations using large systems (24 peptides chains per box) allow us to correctly account for the formation of realistic peptide aggregates. We evaluate the thermodynamic and kinetic implications of changes in sequence and pH upon peptide aggregation, and we discuss how a minimalistic coarse- grained model can account for these details.}, language = {en} } @misc{SchuetteSarich2015, author = {Sch{\"u}tte, Christof and Sarich, Marco}, title = {A Critical Appraisal of Markov State Models}, issn = {1438-0064}, doi = {10.1140/epjst/e2015-02421-0}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-54218}, year = {2015}, abstract = {Markov State Modelling as a concept for a coarse grained description of the essential kinetics of a molecular system in equilibrium has gained a lot of atten- tion recently. The last 10 years have seen an ever increasing publication activity on how to construct Markov State Models (MSMs) for very different molecular systems ranging from peptides to proteins, from RNA to DNA, and via molecu- lar sensors to molecular aggregation. Simultaneously the accompanying theory behind MSM building and approximation quality has been developed well be- yond the concepts and ideas used in practical applications. This article reviews the main theoretical results, provides links to crucial new developments, outlines the full power of MSM building today, and discusses the essential limitations still to overcome.}, language = {en} } @article{AgarwalWangSchuetteetal.2014, author = {Agarwal, Animesh and Wang, Han and Sch{\"u}tte, Christof and Delle Site, Luigi}, title = {Chemical potential of liquids and mixtures via Adaptive Resolution Simulation}, volume = {141}, journal = {The Journal of Chemical Physics}, doi = {10.1063/1.4886807}, pages = {034102}, year = {2014}, language = {en} } @article{KlusGelssPeitzetal.2018, author = {Klus, Stefan and Gelß, Patrick and Peitz, Sebastian and Sch{\"u}tte, Christof}, title = {Tensor-based dynamic mode decomposition}, volume = {31}, journal = {Nonlinearity}, number = {7}, publisher = {IOP Publishing Ltd \& London Mathematical Society}, doi = {10.1088/1361-6544/aabc8f}, year = {2018}, language = {en} } @article{EncisoSchuetteDelleSite2015, author = {Enciso, Marta and Sch{\"u}tte, Christof and Delle Site, Luigi}, title = {Influence of pH and sequence in peptide aggregation via molecular simulation}, volume = {143}, journal = {Journal of Chemical Physics}, number = {24}, doi = {https://doi.org/10.1063/1.4935707}, year = {2015}, language = {en} }