Flexibility-Rigidity Index for Protein-Nucleic Acid Flexibility and Fluctuation Analysis

TL;DR

This paper introduces a multiscale flexibility-rigidity index (FRI) method for analyzing the flexibility of protein-nucleic acid complexes, improving accuracy and efficiency, and applies it to large ribosomal subunits and RNA polymerase dynamics.

Contribution

It extends FRI to multiscale analysis of protein-nucleic acid complexes, enhancing flexibility prediction accuracy and computational efficiency for large biomolecular systems.

Findings

Multiscale FRI significantly improves flexibility analysis accuracy.

The method efficiently analyzes large complexes like ribosomes.

Anisotropic FRI provides insights into RNA polymerase translocation.

Abstract

Protein-nucleic acid complexes are important for many cellular processes including the most essential function such as transcription and translation. For many protein-nucleic acid complexes, flexibility of both macromolecules has been shown to be critical for specificity and/or function. Flexibility-rigidity index (FRI) has been proposed as an accurate and efficient approach for protein flexibility analysis. In this work, we introduce FRI for the flexibility analysis of protein-nucleic acid complexes. We demonstrate that a multiscale strategy, which incorporates multiple kernels to capture various length scales in biomolecular collective motions, is able to significantly improve the state of art in the flexibility analysis of protein-nucleic acid complexes. We take the advantage of the high accuracy and ${\cal O}(N)$ computational complexity of our multiscale FRI method to investigate the flexibility of large ribosomal subunits, which is difficult to analyze by alternative approaches. An anisotropic FRI approach, which involves localized Hessian matrices, is utilized to study the translocation dynamics in an RNA polymerase.