scholarly journals Normal Mode Analysis: A Tool for Better Understanding Protein Flexibility and Dynamics with Application to Homology Models

2020 ◽  
Author(s):  
Jacob A. Bauer ◽  
Vladena Bauerová-Hlinková
Keyword(s):  
Normal Mode ◽  
Protein Complexes ◽  
Normal Mode Analysis ◽  
Computational Cost ◽  
Protein Flexibility ◽  
Systematic Investigation ◽  
Mode Analysis ◽  
Biological Macromolecules ◽  
Elastic Network Model ◽  
Large Proteins

Molecular dynamics (MD) and normal mode analysis (NMA) are very useful methods for characterizing various dynamic aspects of biological macromolecules. In comparison to MD, NMA is computationally less expensive which facilitates the quick and systematic investigation of protein flexibility and dynamics even for large proteins and protein complexes, whose structure was obtained experimentally or in silico. In particular, NMA can be used to describe the flexible states adopted by a protein around an equilibrium position. These states have been repeatedly shown to have biological relevance and functional significance. This chapter briefly characterizes NMA and describes the elastic network model, a schematic model of protein shape used to decrease the computational cost of this method. Finally, we will describe the applications of this technique to several large proteins and their complexes as well as its use in enhancing protein homology modeling.

scholarly journals Normal Mode Analysis as a Routine Part of a Structural Investigation

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3293 ◽  
Author(s):  
Jacob A. Bauer ◽  
Jelena Pavlović ◽  
Vladena Bauerová-Hlinková
Keyword(s):  
Normal Mode ◽  
Structural Study ◽  
Computer Technology ◽  
Structural Investigation ◽  
Normal Mode Analysis ◽  
Computational Cost ◽  
Normal Modes ◽  
Mode Analysis ◽  
Computationally Expensive ◽  
The Web

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.

A complex multiscale virtual particle model based elastic network model (CMVP-ENM) for the normal mode analysis of biomolecular complexes

2019 ◽  
Vol 21 (8) ◽  
pp. 4359-4366 ◽  
Author(s):  
D. Vijay Anand ◽  
Zhenyu Meng ◽  
Kelin Xia
Keyword(s):  
Normal Mode ◽  
Network Model ◽  
Material Properties ◽  
Normal Mode Analysis ◽  
Mode Analysis ◽  
Particle Model ◽  
Elastic Network Model ◽  
Elastic Network ◽  
Virtual Particle ◽  
Biomolecular Complexes

The CMVP-ENM for virus normal mode analysis. With a special ratio parameter, CMVP-ENM can characterize the multi-material properties of biomolecular complexes and systematically enhance or suppress the modes for different components.

scholarly journals STRUCTURE FLUCTUATIONS AND CONFORMATIONAL CHANGES IN PROTEIN BINDING

2012 ◽  
Vol 10 (02) ◽  
pp. 1241002 ◽  
Author(s):  
ANATOLY M. RUVINSKY ◽  
TATSIANA KIRYS ◽  
ALEXANDER V. TUZIKOV ◽  
ILYA A. VAKSER
Keyword(s):  
Conformational Changes ◽  
Protein Complexes ◽  
Normal Mode Analysis ◽  
Distribution Functions ◽  
Mode Analysis ◽  
Amino Acid Type ◽  
Dihedral Angles ◽  
Elastic Network Model ◽  
Centers Of Mass ◽  
Interface Residues

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. Strategies for engineering thermostable proteins are discussed. 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.

scholarly journals A force field for virtual atom molecular mechanics of proteins

2009 ◽  
Vol 106 (37) ◽  
pp. 15667-15672 ◽  
Author(s):  
Anil Korkut ◽  
Wayne A. Hendrickson
Keyword(s):  
Force Field ◽  
Molecular Mechanics ◽  
Normal Mode ◽  
Conformational Changes ◽  
Normal Mode Analysis ◽  
Coarse Grained ◽  
Mode Analysis ◽  
Biological Macromolecules ◽  
Molecular Mechanics Calculations ◽  
Low Degrees

Activities of many biological macromolecules involve large conformational transitions for which crystallography can specify atomic details of alternative end states, but the course of transitions is often beyond the reach of computations based on full-atomic potential functions. We have developed a coarse-grained force field for molecular mechanics calculations based on the virtual interactions of Cα atoms in protein molecules. This force field is parameterized based on the statistical distribution of the energy terms extracted from crystallographic data, and it is formulated to capture features dependent on secondary structure and on residue-specific contact information. The resulting force field is applied to energy minimization and normal mode analysis of several proteins. We find robust convergence in minimizations to low energies and energy gradients with low degrees of structural distortion, and atomic fluctuations calculated from the normal mode analyses correlate well with the experimental B-factors obtained from high-resolution crystal structures. These findings suggest that the virtual atom force field is a suitable tool for various molecular mechanics applications on large macromolecular systems undergoing large conformational changes.

Comparison of all-atom and coarse-grained normal mode analysis in the elastic network model

2013 ◽  
Vol 27 (11) ◽  
pp. 3267-3275 ◽  
Author(s):  
Ming-Wen Hu ◽  
Brian O’Riordan ◽  
Byung Kim ◽  
Moon Ki Kim
Keyword(s):  
Normal Mode ◽  
Network Model ◽  
Normal Mode Analysis ◽  
Coarse Grained ◽  
Mode Analysis ◽  
Elastic Network Model ◽  
Elastic Network

scholarly journals ProMode-Oligomer: Database of Normal Mode Analysis in Dihedral Angle Space for a Full-Atom System of Oligomeric Proteins

2012 ◽  
Vol 6 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Hiroshi Wako ◽  
Shigeru Endo
Keyword(s):  
Normal Mode ◽  
Protein Complexes ◽  
Normal Mode Analysis ◽  
Normal Modes ◽  
Point Of View ◽  
Mode Analysis ◽  
Dihedral Angles ◽  
Oligomeric Proteins ◽  
Displacement Vectors ◽  
Atom System

The database ProMode-Oligomer (http://promode.socs.waseda.ac.jp/promode_oligomer) was constructed by collecting normal-mode-analysis (NMA) results for oligomeric proteins including protein-protein complexes. As in the ProMode database developed earlier for monomers and individual subunits of oligomers (Bioinformatics vol. 20, pp. 2035–2043, 2004), NMA was performed for a full-atom system using dihedral angles as independent variables, and we released the results (fluctuations of atoms, fluctuations of dihedral angles, correlations between atomic fluctuations, etc.). The vibrating oligomer is visualized by animation in an interactive molecular viewer for each of the 20 lowest-frequency normal modes. In addition, displacement vectors of constituent atoms for each normal mode were decomposed into two characteristic motions in individual subunits, i.e., internal and external (deformation and rigid-body movements of the individual subunits, respectively), and then the mutual movements of the subunits and the movement of atoms around the interface regions were investigated. These results released in ProMode-Oligomer are useful for characterizing oligomeric proteins from a dynamic point of view. The analyses are illustrated with immunoglobulin light- and heavy-chain variable domains bound to lysozyme and to a 12-residue peptide.

scholarly journals Deciphering conformational transitions of proteins by small angle X-ray scattering and normal mode analysis

2016 ◽  
Vol 18 (8) ◽  
pp. 5707-5719 ◽  
Author(s):  
Alejandro Panjkovich ◽  
Dmitri I. Svergun
Keyword(s):  
Normal Mode ◽  
Small Angle ◽  
Normal Mode Analysis ◽  
Conformational Transitions ◽  
Scattering Data ◽  
Mode Analysis ◽  
Biological Macromolecules ◽  
X Ray ◽  
X Ray Scattering ◽  
Insight Into

SREFLEX employs normal mode analysis for the flexible refinement of atomic models of biological macromolecules against solution scattering data, providing insight into conformational transitions.

Normal-Mode Analysis Suggests Protein Flexibility Modulation throughout RNA Polymerase's Functional Cycle†

Biochemistry ◽  
2004 ◽  
Vol 43 (41) ◽  
pp. 13083-13096 ◽  
Author(s):  
Adam Van Wynsberghe ◽  
Guohui Li ◽  
Qiang Cui
Keyword(s):  
Normal Mode ◽  
Normal Mode Analysis ◽  
Protein Flexibility ◽  
Mode Analysis

scholarly journals Infrared spectroscopy from electrostatic embedding QM/MM: local normal mode analysis of infrared spectra of arabidopsis thaliana plant cryptochrome

2021 ◽  
Author(s):  
Miquel Huix-Rotllant ◽  
Karno Schwinn ◽  
Nicolas Ferré
Keyword(s):  
Arabidopsis Thaliana ◽  
Infrared Spectroscopy ◽  
Ir Spectra ◽  
Normal Mode ◽  
Infrared Spectra ◽  
Normal Mode Analysis ◽  
Mode Analysis ◽  
Biological Macromolecules ◽  
Electrostatic Embedding

Combined QM/MM Hessians and local normal mode analysis are powerful tools to simulate and interpret complex IR spectra of biological macromolecules.

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