Abstract：
:One tactic for cysteine protease inhibition is to form a covalent bond between an electrophilic atom of the inhibitor and the thiol of the catalytic cysteine. In this study, we evaluate the reaction free energy obtained from a hybrid quantum mechanical/molecular mechanical (QM/MM) free energy profile as a predictor of affinity for reversible, covalent inhibitors of rhodesain. We demonstrate that the reaction free energy calculated with the PM6/MM potential is in agreement with the experimental data and suggest that the free energy profile for covalent bond formation in a protein environment may be a useful tool for the inhibitor design.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
da Costa CHS,Bonatto V,Dos Santos AM,Lameira J,Leitão A,Montanari CAdoi
10.1021/acs.jcim.9b00847subject
Has Abstractpub_date
2020-02-24 00:00:00pages
880-889issue
2eissn
1549-9596issn
1549-960Xjournal_volume
60pub_type
杂志文章abstract：:Given the essential role played by protein kinases in regulating cellular pathways, their dysregulation can result in the onset and/or progression of various human diseases. Structural analysis of diverse protein kinases suggests that these proteins exhibit a remarkable plasticity that allows them to adopt distinct co...
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300382f
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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