Molecular Dynamics (MD) simulations allow us to observe the time-dependent behavior of molecular systems at an atomic level. Unlike static docking models, MD simulations provide a detailed look at the flexibility and conformational changes that occur as host and guest molecules interact in a solvent environment.

By solving Newton’s equations of motion for a system of interacting particles, we can calculate trajectories that reveal the stability of various complexes over nanosecond or microsecond timescales. In our group, @Sofia Moco and others use #MD simulations to study the equilibrium between bound and unbound states, as well as the pathways by which molecules enter and exit host cavities. Recent advancements in force field parameters and hardware acceleration have significantly expanded our ability to model large-scale biological systems and synthetic macrocycles with high precision.

Molecular docking is a vital computational tool used to predict the preferred orientation of a guest molecule within the cavity of host molecules like cyclodextrins. These cyclic oligosaccharides, composed of glucose subunits, possess a unique truncated cone-like structure with a hydrophobic interior and a hydrophilic exterior.

In our recent studies led by @Fanny Beekman, we have utilized various docking algorithms to investigate the binding affinities of different pharmaceutical compounds. Understanding these interactions is crucial for the development of advanced drug delivery systems, where #cyclodextrins serve as carriers to improve the solubility and stability of hydrophobic drugs. By simulating these host-guest complexes, we can gain insights into the thermodynamic favorability and the specific non-covalent interactions, such as van der Waals forces and hydrophobic effects, that drive the inclusion process.