Kinetics of Drug Release from Clay Using Enhanced Sampling Methods.

A key step in the development of a new drug, is the design of drug-excipient complexes that lead to optimal drug release kinetics. Computational chemistry and specifically enhanced sampling molecular dynamics methods can play a key role in this context, by minimizing the need for expensive experiments, and reducing cost and time. Here we show that recent advances in enhanced sampling methodologies can be brought to fruition in this area.

Computing Rates and Understanding Unbinding Mechanisms in Host-Guest Systems.

The long time scale associated with ligand residence times renders their computation challenging. Therefore, the influence of factors like solvation and steric hindrance on residence times is not fully understood. Here, we demonstrate in a set of model host-guest systems that the recently developed Gaussian mixture based enhanced sampling allows residence times to be computed and enables an understanding of their unbinding mechanism.

Gaussian Mixture-Based Enhanced Sampling for Statics and Dynamics.

We introduce an enhanced sampling method that is based on constructing a model probability density from which a bias potential is derived. The model relies on the fact that in a physical system most of the configurations visited can be grouped into isolated metastable islands. With each island we associate a distribution that is fitted to a Gaussian mixture.

Enhanced Sampling of Transition States.

The free energy landscapes of several fundamental processes are characterized by high barriers separating long-lived metastable states. In order to explore these type of landscapes, enhanced sampling methods are used. While many such methods are able to obtain sufficient sampling in order to draw the free energy, the transition states are often sparsely sampled.

Enhanced sampling and free energy calculations with hybrid functionals and plane waves for chemical reactions.

Plane wave basis sets offer many advantages in molecular dynamics due to their efficiency and simplicity. In combination with hybrid density functionals, they become computationally expensive due to the evaluation of the Hartree-Fock exchange energy. The computational cost can be significantly reduced by screening the Kohn-Sham orbital products after localizing the orbitals in real space.