Structural analyses of 2015-updated drug-resistant mutations in HIV-1 protease: an implication of protease inhibitor cross-resistance

Table 3 Structural characterized features used in the graph constructions for the PI-resistance mutants to NFV and SQV

	Vpocket^a (Å³)	AllosComm^b	ΔΔG score / ΔS^c (kcal/mol)	RMSd (Å)
Nelfinavir (NFV) — molecular weight = ~568 g/mol
NFV_0 (wt)	1637.23 (1823.01)	0.584 (0.101)	−1.23 / −0.58	0.6
NFV_1 (major/minor)	1841.98	0.655 (0.403)	2.08 / −0.70	1.09
NFV_2 (minor)	1634.29	0.308 (0.312)	0.62 / −0.63	1.03
NFV_3 (minor)	1669.08	0.795 (0.713)	0.51 / 0.28	0.98
NFV_4 (minor)	1692.91	0.851 (0.713)	0.68 / 0.21	0.98
Saquinavir (SQV) — molecular weight = ~671 g/mol
SQV_0 (minor)	1735.73 (2193.99)	0.735 (0.38)	3.27 / 1.46	0.84
SQV_1 (major/minor)	1700.44	0.787 (0.371)	6.02 / −1.89	0.81
SQV_2 (minor)	1631.92	0.601 (0.346)	0.22 / −0.61	0.82
SQV_3 (minor)	1817.81	0.739 (0.441)	2.14 / 0.72	0.79
SQV_4 (minor)	1531.07	0.748 (0.606)	0.67 / 0.21	0.8

^aPocket volume of the native protease [PDB: 1ODW], which contains no mutations in the presence of corresponding PIs, is shown in parentheses for comparison purpose. In the cases of wild type proteases NFV_0, there is a single mutation found (i.e. V3I) in the structures when compared to the native protease sequence. The complexes that contain the quadruple mutants and show increased pocket volume are in bold
^bFor comparison purposes of allosteric effect, communication estimated values of the native protease were shown in parentheses
^cΔΔG and ΔS scores represent free energy and vibrational energy respectively, demonstrating thermo-stability of the protease when mutated from the native protease

ISSN: 1471-2105