Using protein-ligand docking to assess the chemical tractability of inhibiting a protein target.
Assessing the difficulty of inhibiting a specific protein by a small molecule can be highly valuable in risk-assessment and prioritization of a new target. In particular, when the disease linkage for a number of targets is broadly similar, being able to identify the most tractable can have a significant impact on informing target selection. With an increasing focus against new and novel protein classes, being able to assess the most likely targets to yield lead-like chemical start points can guide the selection and the lead-generation strategy implemented. This study exploits protein-ligand docking studies on published protein x-ray crystal structures to provide guidance on the feasibility of identifying small molecule inhibitors against a range of targets.
Ward
Richard A
RA
Cancer & Infection Discovery, AstraZeneca, Alderley Park, Macclesfield SK104TG, UK. richard.a.ward@astrazeneca.com
D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins
D008024:Ligands; D011506:Proteins