TABLE 1.

Mutations introduced into the RT p51-RNH cleavage site

Abbreviationb	Sequencea (P4-P3′)	Substrate positionb	Classificationc	Commentsd
WT	AETF↓YVD	N/A	N/A	Wild-type sequence
A437I	IETF↓YVD	P4	Radical	Longer P4 to disrupt interactions with PR flap regions
V442S	AETF↓YSD	P2′	Radical	Polar residue substitution
F440W	AETW↓YVD	P1	Conservative	Maintain hydropathicity and scissile bond aromatic symmetry
F440V	AETV↓YVD	P1	Radical	Nonpreferred β-branched residue
T439S/V442G	AESF↓YGD	P2/P2′	Conservative	Diminish side chain interactions of these corroborative positions
Y441I/V442K	AETF↓IKD	P1′/P2′	Radical/Conservative	Disrupt hydropathicity/longer positive residue
F440A	AETA↓YVD	P1	Radical	Nonpreferred small side chain
F440A/Y441A	AETA↓AVD	P1/P1′	Radical	Nonpreferred small side chain
F440W/Y441W	AETW↓WVD	P1/P1′	Conservative	Maintain hydropathicity and scissile bond aromatic symmetry
E438N	ANTF↓YVD	P3	Conservative	Removal of γ-carbonyl to diminish H-bond interactions with PR

^aAmino acid substitutions introduced at various positions flanking the RT p51-RNH scissile bond are in bold italics and are underlined.

^bAbbreviation and substrate position(s) of the mutation(s) are given. N/A, not applicable.

^cConservative or radical mutation based Dayhoff's ranking of functionally conserved amino acid groups, whereby chemical similarity is not necessarily as valuable as size (15).

^dBasis for the mutation with respect to known commonalities and determinants of HIV-1 PR context-dependent specificity (23, 54, 58, 72).