Search of the binding site of the calix[4]arene with the myosin light-chain kinase by molecular dynamics method

A. Zaremba, M. Platonov
Taras Shevchenko National University of Kyiv, Kyiv; Institute of Molecular Biology and Genetics, NAS of Ukraine, Kyiv

Abstract


Disruptions of the functional activity of human smooth muscle are associated with a significant number of pathological conditions of the human body. The myosin light-chain kinase is the key enzyme of the signaling cascade of neurohumoral signals in smooth muscle cells. Especially it is important in the long-term tonic contraction. Disruption of its kinase activity can lead to a weakening of the intercellular interaction of the epithelial and endothelial cells, disruption of functioning of the intestinal smooth muscles and vessels, complication of labor activity. 

At the moment the search for effectors of this enzyme is being carried out. The problem is that most drugs are removed at the general body
level due to toxic effects on other tissues (organs) or adverse chemical and physical properties. Such substances require adapters (carriers) devoid of these defects and inert in vivo. The most promising are calixarenes.

In this study, the molecular dynamics method was used to determine the stability of the calix [4] arenetetrazulphate complex and the myosin
light-chain kinase catalytic domain. Initially, by means of docking, the most favorable position of calixaren was determined; it turned out to be a catalytic kinase pocket. After that, the molecular-dynamic experiment was conducted to determine the energy of interaction. It turned out that the total energy of the interaction is about -300 cJ/mol. This indicates the high stability of the complex. Due the location of the ligand, its effect on the enzymatic activity of the kinase can be assumed, therefore, the use of this calixarene as a drug delivery system seems inappropriate.


Keywords


Disruptions of the functional activity of human smooth muscle are associated with a significant number of pathological conditions of the human body. The myosin light-chain kinase is the key enzyme of the signaling cascade of neurohumoral signals in smooth

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Received: 11.05.2019

Revised: 14.06.2019

Accepted & Published: 14.06.2019




DOI: http://dx.doi.org/10.17721/1728_2748.2019.78.57-61

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