Faster but Not Sweeter: A Model of Escherichia coli Re-level Lipopolysaccharide for Martini 3 and a Martini 2 Version with Accelerated Kinetics

Lipopolysaccharide (LPS) is a complex glycolipid molecule that
is the main lipidic component of the outer leaflet of the outer membrane
of Gram-negative bacteria. It has very limited lateral motion compared
to phospholipids, which are more ubiquitous in biological membranes,
including in the inner leaflet of the outer membrane of Gram-negative
bacteria. The slow-moving nature of LPS can present a hurdle for molecular
dynamics simulations, given that the (pragmatically) accessible timescales
to simulations are currently limited to microseconds, during which
LPS displays some conformational dynamics but hardly any lateral diffusion.
Thus, it is not feasible to observe phenomena such as insertion of
molecules, including antibiotics/antimicrobials, directly into the
outer membrane from the extracellular side nor to observe LPS dissociating
from proteins via molecular dynamics using currently available models
at the atomistic and more coarse-grained levels of granularity. Here,
we present a model of deep rough LPS compatible with the Martini 2
coarse-grained force field with scaled down nonbonded interactions
to enable faster diffusion. We show that the faster-diffusing LPS
model is able to reproduce the salient biophysical properties of the
standard models, but due to its faster lateral motion, molecules are
able to penetrate deeper into membranes containing the faster model.
We show that the fast ReLPS model is able to reproduce experimentally
determined patterns of interaction with outer membrane proteins while
also allowing for LPS to associate and dissociate with proteins within
microsecond timescales. We also complete the Martini 3 LPS toolkit
for Escherichia coli by presenting
a (standard) model of deep rough LPS for this force field.