Efficient Search for Energetically Favorable Molecular Conformations against Metastable States via Gray-Box Optimization

Metastable Conformations via successive Perron-Cluster Cluster Analysis of dihedrals

Decomposition of the high dimensional conformational space of biomolecules into metastable subsets is used for data reduction of long molecular trajectories in order to facilitate chemical analysis and to improve convergence of simulations within these subsets. The metastability is identified by the Perron-Cluster Cluster Analysis of a Markov process that describes the thermodynamic distributio...

Systematic Search of Constrained Molecular Conformations

The Problem: Accurate determination of the three-dimensional atomic structures of molecules is currently a bottleneck in drug design research and is a crucial part of understanding the molecular mechanisms of biological systems. The goal of this project is to systematically enumerate feasible conformations (three-dimensional configurations) of a flexible molecule, subject to a given set of cons...

Predictive Entropy Search for Efficient Global Optimization of Black-box Functions

We propose a novel information-theoretic approach for Bayesian optimization called Predictive Entropy Search (PES). At each iteration, PES selects the next evaluation point that maximizes the expected information gained with respect to the global maximum. PES codifies this intractable acquisition function in terms of the expected reduction in the differential entropy of the predictive distribut...

On Lipschitz optimization based on gray-box piecewise linearization

We address the problem of minimizing objectives from the class of piecewise differentiable functions whose nonsmoothness can be encapsulated in the absolute value function. They possess local piecewise linear approximations with a discrepancy that can be bounded by a quadratic proximal term. This overestimating local model is continuous but generally nonconvex. It can be generated in its abs-no...

Hierarchical Uncoupling-Coupling of Metastable Conformations