4. Experimental Section
We carried out all-atom molecular dynamic simulations (300–500 ns) in
chloroform. Combined with the metadynamics free-energy method, force
field parameters specifically optimized for the quinoline-based
arylamides was calculated by our method [16,17].
This method accelerates the simulation by adding small repulsive
potentials (“hills”) to the underlying free energy landscape, thus
gradually biasing the system to escape energy minima and explore the
wide conformational space. From metadynamics simulations, we determined
the free energy of the oligomers with respect to two Control Variables
(CVs) to generate two-dimensional free free-energy profiles (FEPs). At
least one CV in each metadynamics simulation is chosen to be a pitch
dihedral angle. This angle defined by the centers of masses of four
consecutive quinoline rings (“Q”) (Scheme 1). Identify the handedness
of the helix: a positive dihedral angle for right-handed (P) and a
negative angle for left-handed (M) helices. The metadynamics
computational methods had been successfully used to predict and explain
helix handedness bias in the context of helically folded aromatic
oligoamides in previous reports. All simulations were carried out using
the AMBER-18 package [18].