. Author manuscript; available in PMC: 2019 Jan 27.

Published in final edited form as: J Chem Theory Comput. 2017 Mar 13;13(4):1851–1861. doi: 10.1021/acs.jctc.7b00130

Table 1.

Summary of Modified LJ Terms between Selected Atoms of Probe and Lipid Molecules

			before modification		after modification
interaction sites on molecule 1	interaction site on molecule 2	offset from center of mass of molecule 2 (Å)	$r_{i j}^{\min} (Å)$	$ε_{i j} (\frac{kcal}{mol})$	$r_{i j}^{\min} (Å)$	$ε_{i j} (\frac{kcal}{mol})$
isobutane:CT(CG311)	isobutane:CT(CG311)	0.38	4.00	0.0320	10.0	0.0100
POPC/POPS:C^a(CTL2)	isobutane:CT(CG311)	0.38	4.01	0.0432	10.0	0.0100
POPC/POPS:C^a(CTL2)	isopropyl alcohol:C2(CG311)	0.38	4.01	0.0432	7.00	0.0100
POPC/POPS:C^a(CTL2)	acetamide:C(CG2O1)	0.08	4.00	0.0785	7.00	0.0100
POPC/POPS:C^a(CTL2)	acetate:C2(CG203)	0.10	4.00	0.0626	7.00	0.0100
POPC/POPS:C^a(CTL2)	acetone:C1(CG205)	0.09	4.00	0.0710	7.00	0.0100
POPC/POPS:C^a(CTL2)	DMSO:S2(SG303)	0.44	4.00	0.1400	7.00	0.0100
POPC/POPS:C^a(CTL2)	urea:C2(CG2O6)	0.09	4.00	0.0626	7.00	0.0100

An additional interaction site between each probe molecule and the membrane lipids is introduced to repel probe molecules from the core of the lipid bilayer and from each other if needed. In particular, we chose the location of the interaction site for the repulsion between lipid CLT2 atom (column 1; POPC:C1, C3, C11, C12, C22–C28, C33–C39, C211–C217, C310–C315 and POPS:C1, C3, C11, C22–C28, C33–C39, C211–C217, C310–C315) and a selected atom of each probe molecule (column 2). CGenFF force field atom types of the modified interaction sites are shown in round brackets. Ideally, the chosen interaction site should be located at the center of mass of the probe molecule to reduce any preferred orientation or artificial orientational structure in the density of probes close to the bilayer surface. This is not always possible and requires introducing dummy atoms into the topologies of the probe molecules. As an approximate approach, we chose the closest probe atom to the center of mass. The third column summarizes the actual mismatch between the central atom of each probe molecule and its center of mass. The remaining columns tabulate the modifications in the nonbonded LJ parameters used to keep probes away from the bilayer hydrophobic core or from each other.