. Author manuscript; available in PMC: 2014 Dec 10.

Published in final edited form as: J Chem Theory Comput. 2013 Oct 16;9(12):5693–5705. doi: 10.1021/ct400603p

Table 1.

The cleavage site products and macrocyclic small-molecule inhibitors of HCV NS3/4A Protease

Substrates							Starting structure PDB Code	# of atoms	V_out (Å³)	V_tot (Å³)	vdW kcal/mol
	P6	P5	P4	P3	P2	P1	Starting structure PDB Code	# of atoms	V_out (Å³)	V_tot (Å³)	vdW kcal/mol
3-4A	D	L	E	V	V	T	1CU1	47	341 ± 31	1042±14	−26.9±2.8
4A-4B	D	E	M	E	E	C	3M5M	50	431 ± 40	1097±15	−31.9±2.5
4B-5A	E	C	T	T	P	C	3M5N	43	300 ± 26	950±17	−27.7±2.7
5A-5B	E	D	V	V	C	C	3M5O	44	318 ± 24	993±14	−27.9±2.2

Inhibitors	PDB Code	# of atoms	V_out (Å³)	V_tot (Å³)	vdW kcal/mol
ITMN-191 (Danoprevir)	3M5L	51	567±18	1082±15	−36.5±2.0
MK-5172	3SUD	54	633±20	1165±16	−35.0±2.8
MK-7009 (Vaniprevir)	3SU3	53	606±19	1152±14	−36.6±1.8

V_out: Volume of a cleavage product/inhibitor outside the dynamic substrate envelope

V_tot: Total vdW volume of a cleavage product/inhibitor

vdW: Total vdW contact energy of a cleavage product/inhibitor with the protease