“Virtual patch clamp analysis” for predicting the functional significance of pathogenic variants in sodium channels

N Bielopolski, E Heyman,H Bassan,B BenZeev,M Tzadok, M Ginsberg,L Blumkin, Y Michaeli, R Sokol,N Yosha-Orpaz, R Hady-Cohen,E Banne, D Lev,T Lerman-Sagie, S Wald-Altman,A Nissenkorn

Epilepsy Research(2022)

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摘要
•Mutations on sodium channels genes are leading causes of genetic epilepsy.•The phenotype and treatment are influenced by the type of dysfunction (gain of function GOF vs. loss of function LOF).•Molecular dynamic simulations (MD) studies predict in-silico the function of the mutated protein.•The release time of the sodium ion from the ion sensitivity filter and the pore size were assessed using MD.•Comparison to wild type enabled us to classify the variant as GOF or LOF, providing the clinician information on optional treatments.
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关键词
Epilepsy,Molecular dynamics,Sodium channels,Variant of unknown significance,Selectivity filter
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