1 research outputs found
Comparison of Implicit and Explicit Solvation Models for <i>Iota</i>-Cyclodextrin Conformation Analysis from Replica Exchange Molecular Dynamics
Large
ring cyclodextrins have become increasingly important for
drug delivery applications. In this work, we have performed replica-exchange
molecular dynamics simulations using both implicit and explicit water
solvation models to study the conformational diversity of <i>iota</i>-cyclodextrin containing 14 α-1,4 glycosidic linked d-glucopyranose units (CD14). The new quantifiable calculation
methods are proposed to analyze the openness, bending, and twisted
conformation of CD14 in terms of circularity, biplanar angle, and
one-directional conformation (ODC). CD14 in GB implicit water model
(Igb5) was found mostly in an opened conformation with average circularity
of 0.39 ± 0.16 and a slight bend with average biplanar angle
of 145.5 ± 16.0°. In contrast, CD14 in TIP3P explicit water
solvation is significantly twisted with average circularity of 0.16 ±
0.10, while 29.1% are ODCs. In addition, classification of CD14 conformations
using a Gaussian mixture model (GMM) shows that 85.0% of all CD14
in implicit water at 300 K correspond to the elliptical conformation,
in contrast to 82.3% in twisted form in explicit water. GMM clustering
also reveals minority conformations of CD14 such as the 8-shape, boat-form,
and twisted conformations. This work provides fundamental insights
into CD14 conformation, influence of solvation models, and also proposes
new quantifiable analysis techniques for molecular conformation studies
in the future