Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring.
The ability of molecular docking, using the program Glide and an MM-GBSA postdocking scoring protocol, to correctly rank a number of congeneric kinase inhibitors was assessed. The approach was successful for the cases considered and suggests that this may be useful for the design of inhibitors in the lead optimization phase of drug discovery.
Lyne
Paul D
PD
Cancer Discovery, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham Massachusetts 02451, USA. paul.lyne@astrazeneca.com
Lamb
Michelle L
ML
Saeh
Jamal C
JC
D000814:Aniline Compounds / Q000737:chemistry; D064127:Aurora Kinases; D001665:Binding Sites; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D048057:Mitogen-Activated Protein Kinase 10 / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D009025:Morpholines / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000814:Aniline Compounds; D009025:Morpholines; D010880:Piperidines; D011725:Pyridines; D011743:Pyrimidines; D048057:Mitogen-Activated Protein Kinase 10; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D051357:Cyclin-Dependent Kinase 2; D048051:p38 Mitogen-Activated Protein Kinases