@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} } @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} } @article{SchuetteSarich2015, author = {Sch{\"u}tte, Christof and Sarich, Marco}, title = {A Critical Appraisal of Markov State Models}, volume = {224}, journal = {The European Physical Journal Special Topics}, number = {12}, doi = {10.1140/epjst/e2015-02421-0}, pages = {2445 -- 2462}, 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} } @misc{BittracherBanischSchuette2017, author = {Bittracher, Andreas and Banisch, Ralf and Sch{\"u}tte, Christof}, title = {Data-driven Computation of Molecular Reaction Coordinates}, issn = {1438-0064}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-66179}, year = {2017}, abstract = {The identification of meaningful reaction coordinates plays a key role in the study of complex molecular systems whose essential dynamics is characterized by rare or slow transition events. In a recent publication, the authors identified a condition under which such reaction coordinates exist - the existence of a so-called transition manifold - and proposed a numerical method for their point-wise computation that relies on short bursts of MD simulations. This article represents an extension of the method towards practical applicability in computational chemistry. It describes an alternative computational scheme that instead relies on more commonly available types of simulation data, such as single long molecular trajectories, or the push-forward of arbitrary canonically-distributed point clouds. It is based on a Galerkin approximation of the transition manifold reaction coordinates, that can be tuned to individual requirements by the choice of the Galerkin ansatz functions. Moreover, we propose a ready-to-implement variant of the new scheme, that computes data-fitted, mesh-free ansatz functions directly from the available simulation data. The efficacy of the new method is demonstrated on a realistic peptide system.}, language = {en} } @misc{ZhangSchuette2017, author = {Zhang, Wei and Sch{\"u}tte, Christof}, title = {Reliable approximation of long relaxation timescales in molecular dynamics}, issn = {1438-0064}, doi = {10.3390/e19070367}, url = {http://nbn-resolving.de/urn:nbn:de:0297-zib-63718}, year = {2017}, abstract = {Many interesting rare events in molecular systems like ligand association, protein folding or con- formational changes happen on timescales that often are not accessible by direct numerical simulation. Therefore rare event approximation approaches like interface sampling, Markov state model building or advanced reaction coordinate based free energy estimation have attracted huge attention recently. In this article we analyze the reliability of such approaches: How precise is an estimate of long relaxation timescales of molecular systems resulting from various forms of rare event approximation methods? Our results give a theoretical answer to this question by relating it with the transfer operator approach to molecular dynamics. By doing so they also allow for understanding deep connections between the different approaches.}, language = {en} }