1999 Volume 5 Issue 4 Pages 147-162
Nonsteroidal anti-inflammatory drugs (NSAIDs) which selectively inhibit COX2 without affecting an enzyme activity of COX 1 would be an ideal anti-inflammatory drug. Thus an attempt was made to examine those binding modes of NSAIDs against COX1 and COX2 in terms of hydrogen bond and binding energy by utilizing Dock4.0. It was shown that binding mode to COX2 selective NSAIDs coincided with the result reported in the in vitro study by R.S. Spangler (Seminars in Arthritis and Rheumatism, 26, 435-446 (1996)). Thus, it can be said that there is a fairly good correlation between the Dock4.0 results and those reported in the in vitro study. As far as the binding mode of COX1 selective NSAIDs is concerned one corresponded to the in vitro study reported by R.S. Spangler, another did not and a third presented a mediocre conformity. It was also shown that there existed one to three H-bonds with the net total being at least twelve when NSAIDs such as nabumetone, meclofenamate, niflumic acid, indomethacin, sulindac, and flurbiprofen were bound to COX2. Amino acid residues involved in such hydrogen bonds were Phe A518, Arg A120, Tyr A385, His A90, Tyr A355. Met A522, Ser A353, Gln A192, Leu A352, and Arg A513. Phe A518 and His A90 were reported by R. G. Kurumbail et al. (Nature, 384, 644-648 (1996)) but the rest of the amino acid residues were not.