Normal Mode Analysis as a Routine Part of a Structural Investigation

Abstract

Normal mode analysis (NMA) is a technique that can be used to describe the flexible states accessible to a protein about an equilibrium position. These states have been shown repeatedly to have functional significance. NMA is probably the least computationally expensive method for studying the dynamics of macromolecules, and advances in computer technology and algorithms for calculating normal modes over the last 20 years have made it nearly trivial for all but the largest systems. Despite this, it is still uncommon for NMA to be used as a component of the analysis of a structural study. In this review, we will describe NMA, outline its advantages and limitations, explain what can and cannot be learned from it, and address some criticisms and concerns that have been voiced about it. We will then review the most commonly used techniques for reducing the computational cost of this method and identify the web services making use of these methods. We will illustrate several of their possible uses with recent examples from the literature. We conclude by recommending that NMA become one of the standard tools employed in any structural study.

Recent advances in user-friendly computational tools to engineer protein function

“…3D structure of the protein is supplemented by predicted energy change in DynaMut, and presented along with three other methods: mCSM, DUET [ 143 ] and SDM [ 144 ]. Here we would like to add that NMA is known to have, in some instances, a limited sensitivity to a mutation, unless it is responsible for a substantial conformational change [ 145 ].…”

Dynamics, a Powerful Component of Current and Future in Silico Approaches for Protein Design and Engineering

“…Here, we would like to highlight the availability of tools for rapid analyses of protein allostery focusing on residue-residue interactions in a single static structure or employing normal mode analysis (NMA) to approximate protein dynamics [134]. However, the performances of these approximate tools are often impeded by two factors: (i) the quality of a single-input structure and the extent, to which this structure represents essential interactions present in the conformational ensemble, and (ii) the limited sensitivity of underlying NMA to mutations that do not produce substantial conformational changes [135]. Those limitations are inherently overcome by ensemble-based approaches, in which network analyses of MD simulations are facilitated by the tools discussed in Section 2.1.…”

Development of Putative Isospecific Inhibitors for HDAC6 using Random Forest, QM-Polarized docking, Induced-fit docking, and Quantum mechanics

“…Using Normal mode analysis (NMA) the stability of the induce-fit docked complex, and ease of protein structure deformability was investigated. Using the elastic network model (ENM) [57] method, the degree of deformability of each residue (figure 10i), B-factor obtained from PDB field and NMA mobility data (figure 10ii), eigenvalues representing ease of deforment (figure 10iii), covariance map (figure S7), and elastic network (figure S8) for the docked complex was calculated.…”