Docking studies on kinesin spindle protein inhibitors: an important cooperative 'minor binding pocket' which increases the binding affinity significantly.
Fifteen KSP inhibitors were docked into the receptor and the binding mode was analyzed for the first time. It was considered that in addition to the main binding pocket all the inhibitors merged in, there exists a cooperative minor binding pocket, which could be explored for significantly increased binding affinity. In addition, a good linear relationship between the biological activities and the lowest binding free energies has also been found. This may help in predicting the binding affinity of newly designed KSP inhibitors.
Jiang
Cheng
C
Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang, Nanjing, People's Republic of China.
Chen
Yadong
Y
Wang
Xiaojian
X
You
Qidong
Q
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology; D006860:Hydrogen Bonding; D007211:Indoles / Q000494:pharmacology; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008958:Models, Molecular; D010636:Phenols / Q000494:pharmacology; D011485:Protein Binding; D011743:Pyrimidines / Q000494:pharmacology; D008941:Spindle Apparatus / Q000737:chemistry / Q000187:drug effects*; D013871:Thiones / Q000494:pharmacology
D000596:Amino Acids; C487201:CK0106023; D004224:Diterpenes; C483533:HR22C16; D007211:Indoles; C470243:KIF11 protein, human; D010636:Phenols; D011743:Pyrimidines; D013871:Thiones; C477863:terpendole E; C003724:3-tritylthio-L-alanine; C400223:monastrol; D016547:Kinesins; D003545:Cysteine