Download MendeleyBeta-secretase (BACE-1) inhibitors: accounting for 10s loop flexibility using rigid active sites.
McGaughey, G.B., Colussi, D., Graham, S.L., Lai, M.T., Munshi, S.K., Nantermet, P.G., Pietrak, B., Rajapakse, H.A., Selnick, H.G., Stauffer, S.R., Holloway, M.K.(2007) Bioorg Med Chem Lett 17: 1117-1121
- PubMed: 17112725
- DOI: https://doi.org/10.1016/j.bmcl.2006.11.003
- Primary Citation of Related Structures:
2NTR - PubMed Abstract:
BACE-1 is a flexible enzyme with experimentally determined motion in the flap region, the catalytic aspartates, and the 10s loop. Four in-house crystallographically determined complexes of tertiary carbinamine inhibitors revealed 10s loop motion in the S(3) pocket. These X-ray structures were used to correlate K(i) values, which span over five orders of magnitude, with the calculated interaction energy, using the Merck Molecular Force Field for a series of 19 tertiary carbinamine inhibitors.
Organizational Affiliation:
Department of Molecular Systems, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA. georgia_mcgaughey@merck.com
