Dynamics and modulation studies of human voltage gated Kv1.5 channel

Journal of Biomolecular Structure & Dynamics
Rajabrata Bhuyan, Alpana Seal

Abstract

The voltage gated Kv1.5 channels conduct the ultrarapid delayed rectifier current (IKur) and play critical role in repolarization of action potential duration. It is the most rapidly activated channel and has very little or no inactivated states. In human cardiac cells, these channels are expressed more extensively in atrial myocytes than ventricle. From the evidences of its localization and functions, Kv1.5 has been declared a selective drug target for the treatment of atrial fibrillation (AF). In this present study, we have tried to identify the rapidly activating property of Kv1.5 and studied its mode of inhibition using molecular modeling, docking, and simulation techniques. Channel in open conformation is found to be stabilized quickly within the dipalmitoylphosphatidylcholine membrane, whereas most of the secondary structure elements were lost in closed state conformation. The obvious reason behind its ultra-rapid property is possibly due to the amino acid alteration in S4-S5 linker; the replacement of Lysine by Glutamine and vice versa. The popular published drugs as well as newly identified lead molecules were able to inhibit the Kv1.5 in a very similar pattern, mainly through the nonpolar interactions, and formed sable...Continue Reading

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Citations

Oct 15, 2019·Frontiers in Physiology·Laura Martinez-MateuAdemuyiwa S Aromolaran

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Methods Mentioned

BETA
glycosylation
interaction studies

Software Mentioned

GROMACS
PyMOL
Genetic Optimisation for Ligand Docking ( GOLD ) suite
Structural Analysis and [UNK] Server ( SAVES
Excel
ChemScore
Ligplot
ClustalX
LigPlot +
DS Visualizer

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