Review: Elastic Network Model for Protein Structural Dynamics

Proteins and their complexes undergo conformational changes, which are closely related to their unique biological functions. However, it is of great challenge for both theoretical and experimental studies to resolve the protein conformational changes due to the limitations regarding the time scale, data size and computational cost. In recent years, normal mode analysis based on coarse-grained elastic network model has been proven to be suitable for the study of the collective vibration motions in macromolecules. Based on the topology of native contacts, this coarse-grained analysis can provide the global motions effectively, thus getting insights into the mechanical aspects of proteins dynamics. In this short review, the basic theory and fundamental features of elastic network models are introduced and a wide variety of examples and applications are then discussed.

[1]  M. Levitt,et al.  Molecular dynamics of native protein. I. Computer simulation of trajectories. , 1983, Journal of molecular biology.

[2]  F. Tama,et al.  Flexible multi-scale fitting of atomic structures into low-resolution electron density maps with elastic network normal mode analysis. , 2004, Journal of molecular biology.

[3]  Robert L Jernigan,et al.  Rigid-cluster models of conformational transitions in macromolecular machines and assemblies. , 2005, Biophysical journal.

[4]  K. Hinsen.  Analysis of domain motions by approximate normal mode calculations , 1998, Proteins.

[5]  V. Pande,et al.  Can conformational change be described by only a few normal modes? , 2006, Biophysical journal.

[6]  I. Bahar,et al.  Gaussian Dynamics of Folded Proteins , 1997 .

[7]  Moon Ki Kim,et al.  KOSMOS: a universal morph server for nucleic acids, proteins and their complexes , 2012, Nucleic Acids Res..

[8]  Erik Lindahl,et al.  Refinement of docked protein–ligand and protein–DNA structures using low frequency normal mode amplitude optimization , 2005, Nucleic acids research.

[9]  Ozlem Keskin,et al.  Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies , 2007, BMC Structural Biology.

[10]  G. Hammes.  Multiple conformational changes in enzyme catalysis. , 2002, Biochemistry.

[11]  M. Karplus,et al.  Molecular dynamics and protein function. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Patrice Koehl,et al.  NOMAD-Ref: visualization, deformation and refinement of macromolecular structures based on all-atom normal mode analysis , 2006, Nucleic Acids Res..

[13]  M. DePristo,et al.  Simultaneous determination of protein structure and dynamics , 2005, Nature.

[14]  Bernard R Brooks,et al.  Modeling protein conformational changes by iterative fitting of distance constraints using reoriented normal modes. , 2006, Biophysical journal.

[15]  R. Jernigan,et al.  Global ribosome motions revealed with elastic network model. , 2004, Journal of structural biology.

[16]  J. Kuriyan,et al.  The Conformational Plasticity of Protein Kinases , 2002, Cell.

[17]  Jianpeng Ma,et al.  Normal mode refinement of anisotropic thermal parameters for a supramolecular complex at 3.42-Å crystallographic resolution , 2007, Proceedings of the National Academy of Sciences.

[18]  D. Doyle,et al.  Structural changes during ion channel gating , 2004, Trends in Neurosciences.

[19]  J. Frank,et al.  Dynamic reorganization of the functionally active ribosome explored by normal mode analysis and cryo-electron microscopy , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  N. Go,et al.  Dynamics of a small globular protein in terms of low-frequency vibrational modes. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Martin Zacharias,et al.  Binding site prediction and improved scoring during flexible protein–protein docking with ATTRACT , 2010, Proteins.

[22]  C. Brooks,et al.  Diversity and identity of mechanical properties of icosahedral viral capsids studied with elastic network normal mode analysis. , 2005, Journal of molecular biology.

[23]  D. Koshland,et al.  Comparison of experimental binding data and theoretical models in proteins containing subunits. , 1966, Biochemistry.

[24]  Valentina Tozzini,et al.  Coarse-grained models for proteins. , 2005, Current opinion in structural biology.

[25]  Claudio N. Cavasotto,et al.  Normal mode-based approaches in receptor ensemble docking. , 2012, Methods in molecular biology.

[26]  W. Greenleaf,et al.  Direct observation of base-pair stepping by RNA polymerase , 2005, Nature.

[27]  Martin Karplus,et al.  Large amplitude conformational change in proteins explored with a plastic network model: adenylate kinase. , 2005, Journal of molecular biology.

[28]  P. Prevelige,et al.  High-sensitivity mass spectrometry for imaging subunit interactions: hydrogen/deuterium exchange. , 2004, Current opinion in structural biology.

[29]  I. Bahar,et al.  Coupling between catalytic site and collective dynamics: a requirement for mechanochemical activity of enzymes. , 2005, Structure.

[30]  Konrad Hinsen,et al.  Normal mode-based fitting of atomic structure into electron density maps: application to sarcoplasmic reticulum Ca-ATPase. , 2005, Biophysical journal.

[31]  G. Chirikjian,et al.  Efficient generation of feasible pathways for protein conformational transitions. , 2002, Biophysical journal.

[32]  Sebastian Doniach,et al.  MinActionPath: maximum likelihood trajectory for large-scale structural transitions in a coarse-grained locally harmonic energy landscape , 2007, Nucleic Acids Res..

[33]  N. Go,et al.  Studies on protein folding, unfolding and fluctuations by computer simulation. I. The effect of specific amino acid sequence represented by specific inter-unit interactions. , 2009 .

[34]  E. Demet Akten,et al.  A Docking Study Using Atomistic Conformers Generated via Elastic Network Model for Cyclosporin A/Cyclophilin A Complex , 2009, Journal of biomolecular structure & dynamics.

[35]  F. Tama,et al.  Normal mode based flexible fitting of high-resolution structure into low-resolution experimental data from cryo-EM. , 2004, Journal of structural biology.

[36]  Min Hyeok Kim,et al.  A mass weighted chemical elastic network model elucidates closed form domain motions in proteins , 2013, Protein science : a publication of the Protein Society.

[37]  G. Chirikjian,et al.  Elastic models of conformational transitions in macromolecules. , 2002, Journal of molecular graphics & modelling.

[38]  Dahlia R. Weiss,et al.  Can morphing methods predict intermediate structures? , 2009, Journal of molecular biology.

[39]  M. Wall,et al.  Quantifying allosteric effects in proteins , 2005, Proteins.

[40]  R. Jernigan,et al.  Inter-residue potentials in globular proteins and the dominance of highly specific hydrophilic interactions at close separation. , 1997, Journal of molecular biology.

[41]  M. Kim,et al.  A connection rule for alpha-carbon coarse-grained elastic network models using chemical bond information. , 2006, Journal of molecular graphics & modelling.

[42]  I. Bahar,et al.  Structural changes involved in protein binding correlate with intrinsic motions of proteins in the unbound state. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[43]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[44]  M Levitt,et al.  Molecular dynamics of native protein. II. Analysis and nature of motion. , 1983, Journal of molecular biology.

[45]  Tirion,et al.  Large Amplitude Elastic Motions in Proteins from a Single-Parameter, Atomic Analysis. , 1996, Physical review letters.

[46]  C D Kroenke,et al.  Nuclear magnetic resonance methods for quantifying microsecond-to-millisecond motions in biological macromolecules. , 2001, Methods in enzymology.

[47]  M. Karplus,et al.  Harmonic dynamics of proteins: normal modes and fluctuations in bovine pancreatic trypsin inhibitor. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[48]  K. Swartz,et al.  Towards a structural view of gating in potassium channels , 2004, Nature Reviews Neuroscience.

[49]  M Karplus,et al.  Dynamics of proteins: elements and function. , 1983, Annual review of biochemistry.

[50]  F. Quiocho,et al.  Atomic structure and specificity of bacterial periplasmic receptors for active transport and chemotaxis: variation of common themes , 1996, Molecular microbiology.

[51]  G. Schulz,et al.  The structure of bovine mitochondrial adenylate kinase: Comparison with isoenzymes in other compartments , 1996, Protein science : a publication of the Protein Society.

[52]  Ivet Bahar,et al.  Anisotropic network model: systematic evaluation and a new web interface , 2006, Bioinform..

[53]  Wenjun Zheng,et al.  A unification of the elastic network model and the Gaussian network model for optimal description of protein conformational motions and fluctuations. , 2008, Biophysical journal.

[54]  M. Levitt,et al.  Protein normal-mode dynamics: trypsin inhibitor, crambin, ribonuclease and lysozyme. , 1985, Journal of molecular biology.

[55]  Gregory S Chirikjian,et al.  Efficient determination of low-frequency normal modes of large protein structures by cluster-NMA. , 2005, Journal of molecular graphics & modelling.

[56]  Guang Song,et al.  How well can we understand large-scale protein motions using normal modes of elastic network models? , 2007, Biophysical journal.

[57]  Sebastian Doniach,et al.  Toward the mechanism of dynamical couplings and translocation in hepatitis C virus NS3 helicase using elastic network model , 2007, Proteins.

[58]  Karsten Suhre,et al.  ElNémo: a normal mode web server for protein movement analysis and the generation of templates for molecular replacement , 2004, Nucleic Acids Res..

[59]  Y. Sanejouand,et al.  Conformational change of proteins arising from normal mode calculations. , 2001, Protein engineering.

[60]  G. Phillips,et al.  Optimization and evaluation of a coarse-grained model of protein motion using x-ray crystal data. , 2006, Biophysical journal.

[61]  Joseph A. Bank,et al.  Supporting Online Material Materials and Methods Figs. S1 to S10 Table S1 References Movies S1 to S3 Atomic-level Characterization of the Structural Dynamics of Proteins , 2022 .

[62]  Gregory S Chirikjian,et al.  A Comparison Between Elastic Network Interpolation and MD Simulation of 16S Ribosomal RNA , 2003, Journal of biomolecular structure & dynamics.

[63]  I. Bahar,et al.  Global dynamics of proteins: bridging between structure and function. , 2010, Annual review of biophysics.

[64]  R. Jernigan,et al.  Anisotropy of fluctuation dynamics of proteins with an elastic network model. , 2001, Biophysical journal.

[65]  A. Atilgan,et al.  Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential. , 1997, Folding & design.

[66]  Hassan A. Karimi,et al.  oGNM: online computation of structural dynamics using the Gaussian Network Model , 2006, Nucleic Acids Res..

[67]  Wenjun Zheng,et al.  Predicting order of conformational changes during protein conformational transitions using an interpolated elastic network model , 2010, Proteins.

[68]  Gregory A Voth,et al.  Coarse-grained free energy functions for studying protein conformational changes: a double-well network model. , 2007, Biophysical journal.

[69]  Ivet Bahar,et al.  Maturation dynamics of bacteriophage HK97 capsid. , 2005, Structure.

[70]  Jianpeng Ma,et al.  A New Method for Coarse-Grained Elastic Normal-Mode Analysis. , 2006, Journal of chemical theory and computation.

[71]  A Wlodawer,et al.  Inhibitors of HIV-1 protease: a major success of structure-assisted drug design. , 1998, Annual review of biophysics and biomolecular structure.

[72]  S. Benkovic,et al.  A Perspective on Enzyme Catalysis , 2003, Science.

[73]  Moon Ki Kim,et al.  Using Harmonic Analysis and Optimization to Study Macromolecular Dynamics , 2006 .