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ars-for-ChemRxivF.pdf (2.87 MB)

Modeling the Interplay of Poor Inhibitor Binding and Efficient Formation of a Covalent Adduct upon the Interaction of ARS Compounds with KRASᴳ¹²ᶜ

submitted on 01.09.2019, 10:58 and posted on 04.09.2019, 16:31 by Maria Khrenova, Anna M. Kulakova, Alexander Nemukhin

We contribute to the emerging topic of development of the family of prospective covalent inhibitors of the “undraggable” KRAS protein. Recent experimental studies on the x-ray [Nature 2013; Cell, 2016], in vivo [Cancer Discov., 2016] and in vitro [Nat. Struct. Mol. Biol., 2018] kinetics reached the top of possible detalization of the process. Although many questions on the reaction mechanism still arise. Herein we utilize a set of supercomputer molecular modeling tools and our original strategy on kinetic analysis to evaluate the reaction mechanism of protein-inhibitor interactions to clarify them. Moreover we suggest original strategy to bridge the microscopic calculated parameters with the macroscopic observed ones and compare them.


Russian Science Foundation (project # 19-73-20032)


Email Address of Submitting Author


Lomonosov Moscow State University



ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest


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