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Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations by Julia Subbotina; Vladimir Yarov-Yarovoy; James Lees-Miller; Serdar Durdagi; Jiqing Guo; Henry J. Duff; Sergei Yu. Noskov is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations about?
## Abstract The __hERG1__ gene (Kv11.1) encodes a voltage‐gated potassium channel. Mutations in this gene lead to one form of the Long QT Syndrome (LQTS) in humans. Promiscuous binding of drugs to hERG1 is known to alter the structure/function of the channel leading to an acquired form of the LQTS. Expectably, creation and validation of reliable 3D model of the channel have been a key target in molecular cardiology and pharmacology for the last decade. Although many models were built, they all were limited to pore domain. In this work, a full model of the hERG1 channel is developed which includes all transmembrane segments. We tested a template‐driven __de‐novo__ design with ROSETTA‐membrane modeling using side‐chain placements optimized by subsequent molecular dynamics (MD) simulations. Although backbone templates for the homology modeled parts of the pore and voltage sensors were based on the available structures of KvAP, Kv1.2 and Kv1.2‐Kv2.1 chimera channels, the missing parts are modeled __de‐novo__. The impact of several alignments on the structure of the S4 helix in the voltage‐sensing domain was also tested. Herein, final models are evaluated for consistency to the reported
Who reads Structural refinement of the hERG1 pore and voltage-sensing domains with ROSETTA-membrane and molecular dynamics simulations?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Julia Subbotina; Vladimir Yarov-Yarovoy; James Lees-Miller; Serdar Durdagi; Jiqing Guo; Henry J. Duff; Sergei Yu. Noskov
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); Wiley-Liss Inc; Wiley (ISSN 0887-3585)
- Published
- 2010
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)