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The complexity of molecular kinetics can be reduced significantly by a restriction to metastable conformations which are almost invariant sets of molecular dynamical systems. With the Robust Perron Cl uster Analysis PCCA+, developed by Weber and Deuflhard, we have a tool available which can be used to identify these conformations from a transition probability matrix. This method can also be applied to the corresponding transition rate matrix which provides important information concerning transition pathways of single molecules. In the present paper, we explain the relationship between these tw o concepts and the extraction of conformation kinetics from transition rates. Moreover, we show how transition rates can be approximated and conclude with numerical examples.

The dynamic behavior of molecules can often be described by Markov processes. From computational molecular simulations one can derive transition rates or transition probabilities between subsets of the discretized conformational space. On the basis of this dynamic information, the spatial subsets are combined into a small number of so-called metastable molecular conformations. This is done by clustering methods like the Robust Perron Cluster Analysis (PCCA+). Up to now it is an open question how this coarse graining in space can be transformed to a coarse graining of the Markov chain while preserving the essential dynamic information. In the following article we aim at a consistent coarse graining of transition probabilities or rates on the basis of metastable conformations such that important physical and mathematical relations are preserved. This approach is new because PCCA+ computes molecular conformations as linear combinations of the dominant eigenvectors of the transition matrix which does not hold for other clustering methods.

Whenever the invariant stationary density of metastable dynamical systems decomposes into almost invariant partial densities, its computation as eigenvector of some transition probability matrix is an ill-conditioned problem. In order to avoid this computational difficulty, we suggest to apply an aggregation/disaggregation method which only addresses wellconditioned sub-problems and thus results in a stable algorithm. In contrast to existing methods, the aggregation step is done via a sampling algorithm which covers only small patches of the sampling space. Finally, the theoretical analysis is illustrated by two biomolecular examples.

In this article we aim at an efficient sampling of the stationary distribution of dynamical systems in the presence of metastabilities. In the past decade many sophisticated algorithms have been inven ted in this field. We do not want to simply add a further one. We address the problem that one has applied a sampling algorithm for a dynamical system many times. This leads to different samplings which more or less represent the stationary distribution partially very well, but which are still far away from ergodicity or from the global stationary distribution. We will show how these samplings can be joined together in order to get one global sampling of the stationary distribution.

The identification of metastable conformations of molecules plays an important role in computational drug design. One main difficulty is the fact that the underlying dynamic processes take place in high dimensional spaces. Although the restriction of degrees of freedom to a few dihedral angles significantly reduces the complexity of the problem, the existing algorithms are time-consuming. They are based on the approximation of transition probabilities by an extensive sampling of states according to the Boltzmann distribution. We present a method which can identify metastable conformations without sampling the complete distribution. Our algorithm is based on local transition rates and uses only pointwise information about the potential energy surface. In order to apply the cluster algorithm PCCA+, we compute a few eigenvectors of the rate matrix by the Jacobi-Davidson method. Interpolation techniques are applied to approximate the thermodynamical weights of the clusters. The concluding example illustrates our approach for epigallocatechine, a molecule which can be described by seven dihedral angles.

Wigner transformation provides a one-to-one correspondence between functions on position space (wave functions) and functions on phase space (Wigner functions). Weighted integrals of Wigner functions yield quadratic quantities of wave functions like position and momentum densities or expectation values. For molecular quantum systems, suitably modified classical transport of Wigner functions provides an asymptotic approximation of the dynamics in the high energy regime. The article addresses the computation of Wigner functions by Monte Carlo quadrature. An ad aption of the Metropolis algorithm for the approximation of signed measures with disconnected support is systematically tested in combination with a surface hopping algorithm for non-adiabatic quantum dynamics. The numerical experiments give expectation values and level populations with an error of two to three percent, which agrees with the theoretically expected accuracy.