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Analyzing resistance pattern of non-small cell lung cancer to crizotinib using molecular dynamic approaches

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Title Analyzing resistance pattern of non-small cell lung cancer to crizotinib using molecular dynamic approaches
 
Creator Kumar, Anish
Ramanathan, K
 
Subject Non-small cell lung cancer
Crizotinib resistance
Molecular dynamic simulation
 
Description 23-28
Crizotinib is the
potential anticancer drug used for the treatment of non-small cell lung cancer
(NSCLC) approved by FDA in 2011. The main target for the crizotinib is
anaplastic lymphoma kinase (ALK). Evidences available indicate that double
mutant ALK (L1196M and G1269A) confers resistance to crizotinib. However, how
mutation confers drug resistance is not well-understood. Hence, in the present
study, molecular dynamic (MD) simulation approach was employed to study the
impact of crizotinib binding efficacy with ALK structures at a molecular level.
Docking results indicated that ALK double mutant (L1196M and G1269A)
significantly affected the binding affinity for crizotinib. Furthermore, MD
studies revealed that mutant ALK-crizotinib complex showed higher deviation,
higher fluctuation and decreased number of intermolecular H-bonds, when
compared to the native ALK-crizotinib complex. These results may be immense
importance for the molecular level understanding of the crizotinib resistance
pattern and also for designing potential drug molecule for the treatment of
lung cancer.
 
Date 2015-03-30T04:53:45Z
2015-03-30T04:53:45Z
2015-02
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/31260
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.52(1) [February 2015]