A Finite Element framework for computation of protein normal modes and mechanical response

TL;DR

This paper introduces a finite element-based computational framework for calculating protein normal modes and mechanical responses, enabling efficient analysis of proteins and assemblies with customizable resolution and atomic-level interaction incorporation.

Contribution

It presents a novel finite element method for protein analysis that accommodates arbitrary resolution and includes atomic interactions, improving upon existing models.

Findings

Accurately computes normal modes of proteins and assemblies.

Matches results from all-atom analysis and experiments.

Calculates critical buckling loads under compression.

Abstract

A coarse-grained computational procedure based on the Finite Element Method is proposed to calculate the normal modes and mechanical response of proteins and their supramolecular assemblies. Motivated by the elastic network model, proteins are modeled as homogeneous isotropic elastic solids with volume defined by their solvent-excluded surface. The discretized Finite Element representation is obtained using a surface simplification algorithm that facilitates the generation of models of arbitrary prescribed spatial resolution. The procedure is applied to compute the normal modes of a mutant of T4 phage lysozyme and of filamentous actin, as well as the critical Euler buckling load of the latter when subject to axial compression. Results compare favorably with all-atom normal mode analysis, the Rotation Translation Blocks procedure, and experiment. The proposed methodology establishes a computational framework for the calculation of protein mechanical response that facilitates the incorporation of specific atomic-level interactions into the model, including aqueous-electrolyte-mediated electrostatic effects. The procedure is equally applicable to proteins with known atomic coordinates as it is to electron density maps of proteins, protein complexes, and supramolecular assemblies of unknown atomic structure.