SNIC
SUPR
SNIC SUPR
Allosteric coupling of 6-TM ion channels
Dnr:

SNIC 2018/1-42

Type:

SNAC Large

Principal Investigator:

Lucie Delemotte

Affiliation:

Kungliga Tekniska högskolan

Start Date:

2018-07-01

End Date:

2019-01-01

Primary Classification:

10603: Biophysics

Secondary Classification:

10407: Theoretical Chemistry

Allocation

Abstract

The aim of this proposal is to understand how coupling between allosteric domains occurs in the superfamily of 6-TM voltage-gated like ion channels and to identify the molecular level determinants that support the two coupling mechanisms in different channel families using molecular simulations and evolutionary analysis. This relies on the comparison of large-scale all atom molecular dynamics simulations of ion channels of different members of the superfamily for which the atomistic structures have been resolved very recently and of the amino-acid sequence ensemble making up these various families. Various rigorous data analysis tools rooted in network science will be used to decipher the allosteric signal propagation and to provide a molecular understanding of the signal propagation in these channels. This work serves as a basis for the structure-based design of small molecule drugs that modify the function of these channels, which are drug targets for a variety of diseases (heart arrhythmias, epilepsies, visual impairment...).