Highly Efficient Real-Time TRPV1 Screening Methodology for Effective Drug Candidates

Abstract

Transient receptor potential vanilloid 1 (TRPV1) agonists that bind to the vanilloid pocket are being actively studied in the pharmaceutical industry to develop novel treatments for chronic pain and cancer. To discover synthetic vanilloids without the side effect of capsaicin, a time-consuming process of drug candidate selection is essential to a myriad of chemical compounds. Herein, we propose a novel approach to field-effect transistors for the fast and facile screening of lead vanilloid compounds for the development of TRPV1-targeting medications. The graphene field-effect transistor was fabricated with human TRPV1 receptor protein as the bioprobe, and various analyses (SEM, Raman, and FT-IR) were utilized to verify successful manufacture. Simulations of TRPV1 with capsaicin, olvanil, and arvanil were conducted using AutoDock Vina/PyMOL to confirm the binding affinity. The interaction of the ligands with TRPV1 was detected via the fabricated platform, and the collected responses corresponded to the simulation analysis.

Exploring the taste presentation and receptor perception mechanism of salty peptides from Stropharia rugosoannulata based on molecular dynamics and thermodynamics simulation

“…It is a process based on computational chemistry to pretest and calculates the relationship through computer simulation and realizes mutual recognition of geometric matching and energy matching between biomolecules. In recent years, molecular docking and molecular dynamics simulation have become a way of virtual screening for drug discovery and the search for new targets [27][28][29][30] . Based on molecular docking technology, the rapid screening of taste peptides can be realized, which provides a technical reference in predicting the interaction mechanism between taste peptides and receptors, and analyzing the binding structure of receptors and ligands.…”

Reusable Electronic Tongue Based on Transient Receptor Potential Vanilloid 1 Nanodisc‐Conjugated Graphene Field‐Effect Transistor for a Spiciness‐Related Pain Evaluation

“…Based on the numerical results of the simulation of ligandreceptor binding affinity, the intensity of TRPV1 activation by ligand binding was investigated with a previously fabricated GFET sensor platform. [33][34][35] As those molecules that induce the activation of the TRPV1 channel, spicy food ingredients were selected; such as capsaicin, dihydrocapsaicin, piperine, AITC, and allicin (Figure 3a). These ligands are sources of the major components that induce spicy taste in real food (chili, pepper, wasabi, and garlic).…”

Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain?

“…Thus, overcoming the capsaicin pungency maintaining its properties becomes a challenge. In this sense, capsinoids or non-pungent synthetic analogs of capsaicin, such as olvanil and arvanil (that bind efficiently to TRPV1), could replace capsaicin in some effects [16,17].…”