Structure fluctuations and conformational changes in protein binding

TL;DR

This study classifies protein residues based on their fluctuations and analyzes conformational changes upon binding, revealing insights into protein flexibility, loop regions, and side-chain adjustments during interactions.

Contribution

Introduces a residue classification based on equilibrium fluctuations using normal mode analysis and compares it with B-factor-based methods, highlighting protein flexibility features.

Findings

Loops and disordered regions are highly fluctuating.

Approximately 20% of interface residues change rotamer states upon binding.

Protein association affects dihedral angle distributions depending on amino acid type.

Abstract

Structure fluctuations and conformational changes accompany all biological processes involving macromolecules. The paper presents a classification of protein residues based on the normalized equilibrium fluctuations of the residue centers of mass in proteins and a statistical analysis of conformation changes in the side-chains upon binding. Normal mode analysis and an elastic network model were applied to a set of protein complexes to calculate the residue fluctuations and develop the residue classification. Comparison with a classification based on normalized B-factors suggests that the B-factors may underestimate protein flexibility in solvent. Our classification shows that protein loops and disordered fragments are enriched with highly fluctuating residues and depleted with weakly fluctuating residues. To calculate the dihedral angles distribution functions, the configuration space was divided into cells by a cubic grid. The effect of protein association on the distribution functions depends on the amino acid type and a grid step in the dihedral angles space. The changes in the dihedral angles increase from the near-backbone dihedral angle to the most distant one, for most residues. On average, one fifth of the interface residues change the rotamer state upon binding, whereas the rest of the interface residues undergo local readjustments within the same rotamer.