The recognition mechanism of crizotinib on MTH1: influence of chirality on the bioactivity

Zhou, Shuilian; Wang, Mian; Tong, Zhangfa; Wang, Jianyi

doi:10.1080/00268976.2016.1145750

Cited by 4 publications

(2 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They also utilized a quantitative structure activity relationship (QSAR) model to improve the correlation to 0.88, combining affinities from MMPBSA, QM/MMGBSA, and Glide scoring (Slynko et al, 2014 ). There were other attractive targets including indoleamine 2,3-dioxygenase 1 (Zou et al, 2017 ), translationally controlled tumor protein (Kumar R. et al, 2017 ), estrogen receptor (Anbarasu and Jayanthi, 2017 ), MutT homolog 1 (Zhou et al, 2016 ), survivin (Sarvagalla et al, 2016 ), CD44 (Nguyen et al, 2016 ), calmodulin (Gonzalez-Andrade et al, 2016 ), androgen receptor (Liu H. L. et al, 2016 ), human topoisomerase I (Guruge et al, 2016 ), Mcl-1 (Zhao et al, 2015 ), vascular endothelial growth factor receptor-2 (Wu et al, 2015 ), tubulin (Liao et al, 2014a , b ; Santoshi and Naik, 2014 ; Suri and Naik, 2015 ; Suri et al, 2015 ), the Hsp70 protein family (Bhattacharjee et al, 2015 ; Schneider et al, 2016 ), the Hsp90 protein family (Arba et al, 2015 ), glucose 6-phosphate dehydrogenase (Obiol-Pardo et al, 2014 ; Zhao et al, 2014 ), lysozyme (Zhan et al, 2015 ), p53 (Verma S. et al, 2016 ), wheat germ agglutinin (Parasuraman et al, 2014 ), bromodomains (Muvva et al, 2014 ), matrix metalloproteinases (Zhou et al, 2014 ), protein arginine methyltransferases (Hong et al, 2014 ; Yan et al, 2014 ), human arsenic methyltransferase (Abro and Azam, 2016 ), Atox1 proteins (Wang X. L. et al, 2014 ), tyrosyl-DNA phosphodiesterase 2 (Kossmann et al, 2016 ), and urokinase-type plasminogen activator (Sa et al, 2014 ).…”

Section: Applications Of Mmpbsamentioning

confidence: 99%

Recent Developments and Applications of the MMPBSA Method

Wang

Greene

Xiao

et al. 2018

Front. Mol. Biosci.

467

327

View full text Add to dashboard Cite

The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been widely applied as an efficient and reliable free energy simulation method to model molecular recognition, such as for protein-ligand binding interactions. In this review, we focus on recent developments and applications of the MMPBSA method. The methodology review covers solvation terms, the entropy term, extensions to membrane proteins and high-speed screening, and new automation toolkits. Recent applications in various important biomedical and chemical fields are also reviewed. We conclude with a few future directions aimed at making MMPBSA a more robust and efficient method.

show abstract

Section: Applications Of Mmpbsamentioning

confidence: 99%

Recent Developments and Applications of the MMPBSA Method

Wang

Greene

Xiao

et al. 2018

Front. Mol. Biosci.

467

327

View full text Add to dashboard Cite

show abstract

“…Niu and co-workers illuminated that Tyr7, Phe27, Phe72 and Trp117 were significant for the selective inhibition of (S)-crizotinib on MTH116. Zhou and co-workers demonstrated that (S)-crizotinib could induce larger conformation fluctuation on MTH1 than (R)-crizotinib17.…”

mentioning

confidence: 99%

Understanding the molecular mechanism for the differential inhibitory activities of compounds against MTH1

Wang

Zhou

Chen

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

MTH1 can hydrolyze oxidized nucleotides and is required for cancer survival. The IC50 values were 0.8 nM for TH287 with a methyl substitution, 5.0 nM for TH588 with a cyclopropyl substitution, and 2.1 μM for TH650 with an oxetanyl substitution. Thus, it is very significant to understand inhibitory mechanisms of these structurally similar compounds against MTH1 and influences of the substituent on the bioactivities. Our MD researches indicate that TH287 maintains significant hydrogen bonds with Asn33 and Asp119, stabilizes the binding site, and induces MTH1 adopt a closed motion, leading to a high inhibitory activity. When bound with TH588, the binding site can be partially stabilized and take a semi-closed state, which is because the cyclopropyl group in TH588 has larger steric hindrance than a methyl group in TH287. So TH588 has a slightly reduced inhibitory activity compared to TH287. TH650 induces greater conformation fluctuations than TH588 and the binding site adopts an opening state, which is caused by the large bulk of oxetanyl group and the interference of solvent on the oxetanyl substituent, leading to the lowest inhibitory activity. Thus, the inhibitory activity follows a TH287 > TH588 > TH650 trend, which well matches with the experimental finding.

show abstract