Food-derived linear vs. rationally designed cyclic peptides as potent TNF-alpha inhibitors: an integrative computational study.

ABSTRACT:

Introduction

Tumor necrosis factor-alpha (TNF-alpha) is a central mediator of chronic inflammation and a validated therapeutic target in atherosclerosis and related cardiovascular disorders. Peptide therapeutics offer high specificity and low toxicity; however, few natural sequences have been optimized for durable TNF-alpha inhibition.

Methods

A dual in silico strategy was employed to identify potent inhibitors: (i) virtual screening of experimentally validated food-derived bioactive peptides and (ii) rational design of an N-C cyclized and disulfide-bridge peptide based on the TNF-alpha-TNFR1 interface. Molecular docking, 200-ns molecular dynamics simulations, and MM/PBSA free-energy analyses were performed.

Results

The selected peptides exhibited strong and persisten

SUBMITTER: Shah M 

PROVIDER: S-EPMC12669231 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature