Uncertainty quantification of receptor ligand binding sites prediction.

Recent advancements in protein docking site prediction have highlighted the limitations of traditional rigid docking algorithms, like PIPER, which often neglect critical stochastic elements such as solvent-induced fluctuations. These oversights can lead to inaccuracies in identifying viable docking sites due to the complexity of high-dimensional, stochastic energy manifolds with low regularity. To address this issue, our research introduces a novel model where the molecular shapes of ligands and receptors are represented using multi-variate Karhunen-Lo `eve (KL) expansions. This method effectively captures the stochastic nature of energy manifolds, allowing for a more accurate representation of molecular interactions.Developed as a plugin for PIPER, our scientific computing software enhances the platform, delivering robust uncertainty measures for the energy manifolds of ranked binding sites. Our results demonstrate that top-ranked binding sites, characterized by lower uncertainty in the stochastic energy manifold, align closely with actual docking sites. Conversely, sites with higher uncertainty correlate with less optimal docking positions. This distinction not only validates our approach but also sets a new standard in protein docking predictions, offering substantial implications for future molecular interaction research and drug development.

A hybrid collocation-perturbation approach for PDEs with random domains.

Consider a linear elliptic PDE defined over a stochastic stochastic geometry a function of N random variables. In many application, quantify the uncertainty propagated to a Quantity of Interest (QoI) is an important problem. The random domain is split into large and small variations contributions. The large variations are approximated by applying a sparse grid stochastic collocation method. The small variations are approximated with a stochastic collocation-perturbation method and added as a correction term to the large variation sparse grid component. Convergence rates for the variance of the QoI are derived and compared to those obtained in numerical experiments. Our approach significantly reduces the dimensionality of the stochastic problem making it suitable for large dimensional problems. The computational cost of the correction term increases at most quadratically with respect to the number of dimensions of the small variations. Moreover, for the case that the small and large variations are independent the cost increases linearly.

A stochastic collocation approach for parabolic PDEs with random domain deformations.

In this article we analyze the linear parabolic partial differential equation with a stochastic domain deformation. In particular, we concentrate on the problem of numerically approximating the statistical moments of a given Quantity of Interest (QoI). The geometry is assumed to be random. The parabolic problem is remapped to a fixed deterministic domain with random coefficients and shown to admit an extension on a well defined region embedded in the complex hyperplane. The stochastic moments of the QoI are computed by employing a collocation method in conjunction with an isotropic Smolyak sparse grid. Theoretical sub-exponential convergence rates as a function to the number of collocation interpolation knots are derived. Numerical experiments are performed and they confirm the theoretical error estimates.

Analytic regularity and stochastic collocation of high-dimensional Newton iterates.

In this paper we introduce concepts from uncertainty quantification (UQ) and numerical analysis for the efficient evaluation of stochastic high dimensional Newton iterates. In particular, we develop complex analytic regularity theory of the solution with respect to the random variables. This justifies the application of sparse grids for the computation of statistical measures. Convergence rates are derived and are shown to be subexponential or algebraic with respect to the number of realizations of random perturbations. Due the accuracy of the method, sparse grids are well suited for computing low probability events with high confidence. We apply our method to the power flow problem. Numerical experiments on the non-trivial 39 bus New England power system model with large stochastic loads are consistent with the theoretical convergence rates. Moreover, compared to the Monte Carlo method our approach is at least 1011 times faster for the same accuracy.

Compressed representations of macromolecular structures and properties.

We introduce a new and unified, compressed volumetric representation for macromolecular structures at varying feature resolutions, as well as for many computed associated properties. Important caveats of this compressed representation are fast random data access and decompression operations. Many computational tasks for manipulating large structures, including those requiring interactivity such as real-time visualization, are greatly enhanced by utilizing this compact representation. The compression scheme is obtained by using a custom designed hierarchical wavelet basis construction. Due to the continuity offered by these wavelets, we retain very good accuracy of molecular surfaces, at very high compression ratios, for macromolecular structures at multiple resolutions.