A Random Force is a Force, of Course, of Coarse: Decomposing Complex Enzyme Kinetics with Surrogate Models

The temporal autocorrelation (AC) function associated with monitoring order parameters characterizing conformational fluctuations of an enzyme is analyzed using a collection of surrogate models. The surrogates considered are phenomenological stochastic differential equation (SDE) models. It is demonstrated how an ensemble of such surrogate models, each surrogate being calibrated from a single trajectory, indirectly contains information about unresolved conformational degrees of freedom. This ensemble can be used to construct complex temporal ACs associated with a "non-Markovian" process. The ensemble of surrogates approach allows researchers to consider models more flexible than a mixture of exponentials to describe relaxation times and at the same time gain physical information about the system. The relevance of this type of analysis to matching single-molecule experiments to computer simulations and how more complex stochastic processes can emerge from a mixture of simpler processes is also discussed. The ideas are illustrated on a toy SDE model and on molecular dynamics simulations of the enzyme dihydrofolate reductase.Comment: 11 pages / 6 figure

Estimating eddy diffusivities from noisy Lagrangian observations

The problem of estimating the eddy diffusivity from Lagrangian observations in the presence of measurement error is studied in this paper. We consider a class of incompressible velocity fields for which is can be rigorously proved that the small scale dynamics can be parameterised in terms of an eddy diffusivity tensor. We show, by means of analysis and numerical experiments, that subsampling of the data is necessary for the accurate estimation of the eddy diffusivity. The optimal sampling rate depends on the detailed properties of the velocity field. Furthermore, we show that averaging over the data only marginally reduces the bias of the estimator due to the multiscale structure of the problem, but that it does significantly reduce the effect of observation error

Sparse Non Gaussian Component Analysis by Semidefinite Programming

Sparse non-Gaussian component analysis (SNGCA) is an unsupervised method of extracting a linear structure from a high dimensional data based on estimating a low-dimensional non-Gaussian data component. In this paper we discuss a new approach to direct estimation of the projector on the target space based on semidefinite programming which improves the method sensitivity to a broad variety of deviations from normality. We also discuss the procedures which allows to recover the structure when its effective dimension is unknown

Markov chain Monte Carlo for exact inference for diffusions

We develop exact Markov chain Monte Carlo methods for discretely-sampled, directly and indirectly observed diffusions. The qualification "exact" refers to the fact that the invariant and limiting distribution of the Markov chains is the posterior distribution of the parameters free of any discretisation error. The class of processes to which our methods directly apply are those which can be simulated using the most general to date exact simulation algorithm. The article introduces various methods to boost the performance of the basic scheme, including reparametrisations and auxiliary Poisson sampling. We contrast both theoretically and empirically how this new approach compares to irreducible high frequency imputation, which is the state-of-the-art alternative for the class of processes we consider, and we uncover intriguing connections. All methods discussed in the article are tested on typical examples.Comment: 23 pages, 6 Figures, 3 Table

Sequential Change Point Detection in Molecular Dynamics Trajectories

Motivated from a molecular dynamics context we propose a sequential change point detection algorithm for vector-valued autoregressive models based on Bayesian model selection. The algorithm does not rely on any sampling procedure or assumptions underlying the dynamics of the transitions and is designed to cope with high-dimensional data. We show the applicability of the algorithm on a time series obtained from numerical simulation of a penta-peptide molecule