# Temporal complexity of LVV-hemorphin-7 allosterism at the angiotensin II type 1 receptor assessed using entropy-based approaches

## TL;DR

This study explores how the peptide LVV-H7 affects the angiotensin II receptor using entropy-based methods, revealing dynamic and pathway-specific modulation.

## Contribution

The study introduces entropy-based approaches to analyze the temporal complexity of LVV-H7's allosteric effects on a receptor.

## Key findings

- LVV-H7 increases signaling complexity when used alone and stabilizes receptor activity when combined with angiotensin II.
- The effects of LVV-H7 differ between the Gαq and β-arrestin signaling pathways.
- Entropy-based tools reveal dynamic and pathway-specific receptor behavior modulated by LVV-H7.

## Abstract

Allosteric modulation constitutes an interesting aspect of the molecular pharmacology of hormone receptors and enzymes with implications in basic research and drug discovery. The modulation of the angiotensin II type 1 receptor by the endogenous peptide, LVV-hemorphin 7 (LVV-H7), is an example that was recently reported using various in vitro pharmacological and biochemical approaches as well as in silico analysis. In this study, we used real-time biosensor data using BRET technology and applied sample entropy and multiscale Rényi entropy to measure the effect of LVV-H7 on receptor activity over time. LVV-H7 increased signaling complexity when used alone and stabilized receptor activity when combined with angiotensin II. These effects were different for the Gαq and β-arrestin signaling pathways. The results indicate that LVV-H7 functions to fine-tunes receptor behavior in a dynamic and pathway-specific manner. This highlights the value of entropy-based tools for tracking changes in cell signaling and further exploring hormone receptor pharmacology and signaling with potential applications in drug design and analysis. The study also suggests that endogenous peptides such as LVV-H7 could offer new ways to modulate the angiotensin II receptor for therapeutic benefit.

•Our findings link statistical physics of entropy to receptor pharmacology and drug design.•The entropy-based analysis identified time-varying complexity in GPCR signaling.•LVV-Hemorphin-7 has the potential to modulate the AT1 receptor by dynamic and pathway-specific mechanisms.•Sample entropy and multiscale Rényi entropy describe configurational transitions of the receptor specific to ligand binding.•LVV-H7 enhances AngII binding, stabilizes receptor dynamics and indicates change in receptor configurational dynamics.

Our findings link statistical physics of entropy to receptor pharmacology and drug design.

The entropy-based analysis identified time-varying complexity in GPCR signaling.

LVV-Hemorphin-7 has the potential to modulate the AT1 receptor by dynamic and pathway-specific mechanisms.

Sample entropy and multiscale Rényi entropy describe configurational transitions of the receptor specific to ligand binding.

LVV-H7 enhances AngII binding, stabilizes receptor dynamics and indicates change in receptor configurational dynamics.