TY - JOUR
T1 - Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase
AU - Jorgensen, William L.
AU - Ruiz-Caro, Juliana
AU - Tirado-Rives, Julian
AU - Basavapathruni, Aravind
AU - Anderson, Karen S.
AU - Hamilton, Andrew D.
N1 - Funding Information:
Gratitude is expressed to the National Institutes of Health (AI44616, GM32136, GM35208, and GM49551) for support.
PY - 2006/2/1
Y1 - 2006/2/1
N2 - Design principles are delineated for non-nucleoside inhibitors for HIV-1 reverse transcriptase (NNRTIs). Simultaneous optimization of binding affinity for wild-type RT, tolerance for viral mutations, and physical properties is pursued. Automated lead generation with the growing program BOMB, Monte Carlo simulations with free-energy perturbation theory for lead optimization, and property analysis with QikProp are featured. An initial 30 μM lead has been optimized rapidly to the 10 nM level.
AB - Design principles are delineated for non-nucleoside inhibitors for HIV-1 reverse transcriptase (NNRTIs). Simultaneous optimization of binding affinity for wild-type RT, tolerance for viral mutations, and physical properties is pursued. Automated lead generation with the growing program BOMB, Monte Carlo simulations with free-energy perturbation theory for lead optimization, and property analysis with QikProp are featured. An initial 30 μM lead has been optimized rapidly to the 10 nM level.
KW - Anti-HIV drugs
KW - Computer-aided drug design
KW - NNRTI
KW - Structure-based drug design
UR - http://www.scopus.com/inward/record.url?scp=29544447433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=29544447433&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2005.10.038
DO - 10.1016/j.bmcl.2005.10.038
M3 - Article
C2 - 16263277
AN - SCOPUS:29544447433
VL - 16
SP - 663
EP - 667
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 3
ER -