Bernd Ensing

Lars Holdijk, Yuanqi Du, Ferry Hooft et al.

We consider the problem of sampling transition paths between two given metastable states of a molecular system, e.g. a folded and unfolded protein or products and reactants of a chemical reaction. Due to the existence of high energy barriers separating the states, these transition paths are unlikely to be sampled with standard Molecular Dynamics (MD) simulation. Traditional methods to augment MD with a bias potential to increase the probability of the transition rely on a dimensionality reduction step based on Collective Variables (CVs). Unfortunately, selecting appropriate CVs requires chemical intuition and traditional methods are therefore not always applicable to larger systems. Additionally, when incorrect CVs are used, the bias potential might not be minimal and bias the system along dimensions irrelevant to the transition. Showing a formal relation between the problem of sampling molecular transition paths, the Schrödinger bridge problem and stochastic optimal control with neural network policies, we propose a machine learning method for sampling said transitions. Unlike previous non-machine learning approaches our method, named PIPS, does not depend on CVs. We show that our method successful generates low energy transitions for Alanine Dipeptide as well as the larger Polyproline and Chignolin proteins.

Jim Boelrijk, Bernd Ensing, Patrick Forré

Optimizing multiple competing objectives is a common problem across science and industry. The inherent inextricable trade-off between those objectives leads one to the task of exploring their Pareto front. A meaningful quantity for the purpose of the latter is the hypervolume indicator, which is used in Bayesian Optimization (BO) and Evolutionary Algorithms (EAs). However, the computational complexity for the calculation of the hypervolume scales unfavorably with increasing number of objectives and data points, which restricts its use in those common multi-objective optimization frameworks. To overcome these restrictions we propose to approximate the hypervolume function with a deep neural network, which we call DeepHV. For better sample efficiency and generalization, we exploit the fact that the hypervolume is scale-equivariant in each of the objectives as well as permutation invariant w.r.t. both the objectives and the samples, by using a deep neural network that is equivariant w.r.t. the combined group of scalings and permutations. We evaluate our method against exact, and approximate hypervolume methods in terms of accuracy, computation time, and generalization. We also apply and compare our methods to state-of-the-art multi-objective BO methods and EAs on a range of synthetic benchmark test cases. The results show that our methods are promising for such multi-objective optimization tasks.