Application of a novel in silico high-throughput screen to identify selective inhibitors for protein-protein interactions.
Increasing numbers of target protein structures available for computational studies makes the structure-based screening paradigm more attractive for initial hit indentification. We have developed a novel in silico screening methodology incorporating Molecular Mechanics (MM)/implicit solvent methods to evaluate binding free energies and applied this technology to the identification of inhibitors of the TLR4/MD-2 interaction.
Joce
Catherine
C
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, CO 80309, USA.
Stahl
Joshua A
JA
Shridhar
Mitesh
M
Hutchinson
Mark R
MR
Watkins
Linda R
LR
Fedichev
Peter O
PO
Yin
Hang
H
D000818:Animals; D002460:Cell Line; D015195:Drug Design; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding / Q000187:drug effects; D025941:Protein Interaction Mapping / Q000379:methods*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D051197:Toll-Like Receptor 4