ACE inhibitor features investigated. Position of features shown in 2D relation to one another. Blue circles surround atoms studied for activity.

Chemical structures of folates and antifolates. A) folic acid (DHFR substrate). B) methotrexate (classical antifolate DHFR inhibitor). C) trimetrexate (non-classical antifolate DHFR inhibitor).

Comparison of the S1' sub-site residues which bind the lysyl group of lisinopril. A) tACE (green) [22] and B) the N-terminal domain of sACE (purple) [29]. Colour scheme is identical to Figure 1.

DHFR inhibitor features investigated. Position of features shown in 2D relation to one another. Blue circles surround atoms which were studied for activity. Methoxy groups located at all positions of the benzyl ring were studied.

Conserved ACE residues that interact with lisinopril. A) tACE active site (green) [22]. B) The N-domain active site of sACE (purple) [29]. Zinc ion shown in magenta; atoms are coloured as follows: red for oxygen, blue for nitrogen, cyan for carbon and grey for hydrogen.

TMACC interpretation of ACE inhibitors. TMACC activity colour scheme: red for very negative activity; orange for negative activity; green for neutral activity; yellow for positive activity and blue for very positive activity. A) molecule 87, captopril; the sulfhydryl zinc binding group, P1' methyl group, central carbonyl and the C-terminal carboxylate are all shown in blue, indicating that they provide a positive contribution to the activity of the molecule. B) molecule 64, enalaprilat; the carboxylate zinc binding group, P1' methyl group, central carbonyl and the C-terminal carboxylate are all shown to provide a positive contribution to the activity of the molecule. C) molecule 65, lisinopril; the carboxylate zinc binding group, P1' lysyl group, central carbonyl and the C-terminal carboxylate all provide a positive contribution to the activity of the molecule.

TMACC interpretation of DHFR inhibitors. TMACC activity colour scheme: red for very negative activity; orange for negative activity; green for neutral ctivity; yellow for positive activity and blue for very positive activity. A) Molecule 202; the 2-amino group, N1 nitrogen and N8 nitrogen are shown to provide a negative contribution to the activity of the molecule. The 4-amino group, 5 methyl, 10 methyl and the methyl group of the benzylmethoxy are all shown to provide a positive contribution to the activity of the molecule. B) molecule 22, trimetrexate; the 2-amino group and N1 nitrogen are both shown to provide a negative contribution to the activity of the molecule. The 4-amino group, 5 methyl, C8 carbon and the methyl groups of the benzylmethoxy groups are all shown to provide a positive contribution to the activity of the molecule. C) molecule 189; the 2-amino group, N1 nitrogen and N8 nitrogen are shown to contribute negatively to the activity of the molecule. The 4-amino, 9 methyl and the methyl groups of the benzylmethoxy groups are all shown to provide a positive contribution to the activity of the molecule.