PDB-NMA of a Protein Homodimer Reproduces Distinct Experimental Motility Asymmetry

TL;DR

This study extends PDB-NMA to protein dimers, successfully reproducing experimental motility asymmetry and revealing how structure influences vibrational properties, providing insights into dimer interactions and catalytic mechanisms.

Contribution

We developed an extended PDB-NMA method for protein dimers that accurately reproduces experimental motility asymmetry and offers a mechanical perspective on subunit interactions.

Findings

Reproduces experimental motility asymmetry in a homodimer

Shows structure influences vibrational signatures

Suggests a mechanical model for subunit interconversion

Abstract

We have extended our analytically derived PDB-NMA formulation, ATMAN [1], to include protein dimers using mixed internal and Cartesian coordinates. A test case on a 1.3\AA\ resolution model of a small homodimer, ActVA-ORF6, consisting of two 112-residue subunits identically folded in a compact 50\AA\ sphere, reproduces the distinct experimental Debye-Waller motility asymmetry for the two chains, demonstrating that structure sensitively selects vibrational signatures. The vibrational analysis of this PDB entry, together with biochemical and crystallographic data, demonstrates the cooperative nature of the dimeric interaction of the two subunits and suggests a mechanical model for subunit interconversion during the catalytic cycle.