Computational Design of High-Affinity Blockers for Sodium Channel Na_V1.2 from μ-Conotoxin KIIIA.

ABSTRACT: The voltage-gated sodium channel subtype 1.2 (Na_V1.2) is instrumental in the initiation of action potentials in the nervous system, making it a natural drug target for neurological diseases. Therefore, there is much pharmacological interest in finding blockers of Na_V1.2 and improving their affinity and selectivity properties. An extensive family of peptide toxins from cone snails (conotoxins) block Na_V channels, thus they provide natural templates for the design of drugs targeting Na_V channels. Unfortunately, progress was hampered due to the absence of any Na_V structures. The recent determination of cryo-EM structures for Na_V channels has finally broken this impasse. Here, we use the Na_V1.2 structure in complex wi

SUBMITTER: Meng G 

PROVIDER: S-EPMC8880641 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature