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].