Article
Potency-Enhancing Mutations of Gating Modifier Toxins for the Voltage-Gated Sodium Channel NaV1.7 Can Be Predicted Using Accurate Free-Energy Calculations.
Toxins - 7 Mar 2021
Katz Dana, Sindhikara Dan, DiMattia Michael, Leffler Abba E
Abstract excerpt
Gating modifier toxins (GMTs) isolated from venomous organisms such as Protoxin-II (ProTx-II) and Huwentoxin-IV (HwTx-IV) that inhibit the voltage-gated sodium channel NaV1.7 by binding to its voltage-sensing domain II (VSDII) have been extensively investigated as non-opioid analgesics. However, reliably predicting how a mutation to a GMT will affect its potency for NaV1.7 has been challenging. Here, we...
Topics
- Binding Sites
- Computer Simulation
- Cryoelectron Microscopy
- Ion Channel Gating
- Models, Molecular
- Mutation
- NAV1.7 Voltage-Gated Sodium Channel
- Peptides
- Protein Binding
- Protein Conformation
- Spider Venoms
- Structure-Activity Relationship
- Voltage-Gated Sodium Channel Blockers