Structure-Guided Discovery of Benzoic-Acid-Based TRPC6 Ligands: An Integrated Docking, MD, and MM-GBSA SAR Study: Potential Therapeutic Molecules for Autism Spectrum Disorder.

ABSTRACT: Background: TRPC6 is recognized as a therapeutically relevant cation channel, whose activation is governed by specific ligand-pocket interactions. Methods: An integrated in silico workflow was employed, comprising structure-based docking, 100-nanosecond molecular dynamics (MD) simulations, and MM-GBSA calculations. Benzoic-acid-based compounds were designed and prioritized for binding to the TRPC6 pocket, using a known literature agonist as a reference for benchmarking. Results: Within the compound series, BT11 was found to exhibit a representative interaction profile, characterized by a key hydrogen bond with Trp680 (~64% occupancy), persistent salt-bridge interactions with Lys676 and Lys698, and π-π stacking with Phe675 and Phe679. A favorable docking score (-11.45 k

SUBMITTER: Silva NI 

PROVIDER: S-EPMC12566912 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature