Table 2. Rationale for NPC1L1 domain interface mutants generated.

Residue	Residues in other domains within 5 Å	Type of interaction	Mutation chosen
A179	L523, Y524, N527	Hydrophobic/hydrophilic	K (possibly trigger steric clash and disrupt the interface)
L427	A180	van der waals/hydrophobic	N (possibly disrupt the hydrophobic interface)
N527	R112, Q257	Hydrophilic	D (could stabilize the interface, restricting domain flexibility); K (potentially destabilize the interface because of positive charge repulsion)
K533	K1026	Electrostatic	E (could stabilize and restrict domain flexibility)
E939	P549, F551	van der waals	K (longer sidechain might result in steric clash, disrupt the interface)
R1002	D250	Electrostatic	E (possibly disrupt the interface)
K1026	K533	Electrostatic	R (possibly stabilize the interface and restrict domain flexibility)
L1029	L530, M543	van derwaals/hydrophobic	N (possibly disrupt the interface)
L987	I72	van derwaals/hydrophobic	N (possibly disrupt the interface)