# Rigidity strengthening is a vital mechanism for protein-ligand binding

## TL;DR

This paper demonstrates that protein rigidity strengthening and reduced flexibility are key mechanisms in protein-ligand binding, with implications for drug and protein design, and introduces a rigidity-based approach that outperforms existing scoring functions.

## Contribution

The study reveals a long-range contribution of residue layers to binding and highlights the importance of short-range interactions, advancing understanding of binding mechanisms.

## Key findings

- Rigidity strengthening is crucial in protein-ligand binding.
- Residue layers contribute significantly to binding affinity.
- The proposed rigidity-based method outperforms existing scoring functions.

## Abstract

Protein-ligand binding is essential to almost all life processes. The understanding of protein-ligand interactions is fundamentally important to rational drug design and protein design. Based on large scale data sets, we show that protein rigidity strengthening or flexibility reduction is a pivoting mechanism in protein-ligand binding. Our approach based solely on rigidity is able to unveil a surprisingly long range contribution of four residue layers to protein-ligand binding, which has a ramification for drug and protein design. Additionally, the present work reveals that among various pairwise interactions, the short range ones within the distance of the van der Waals diameter are most important. It is found that the present approach outperforms all the other state-of-the-art scoring functions for protein-ligand binding affinity predictions of two benchmark data sets