Elastic Image Registration To Fully Explore Macromolecular Dynamics By Electron Microscopy Qiyu Jin 1 , Carlos Oscar Sanchez Sorzano 2 , Isabelle Callebaut 1 , Florence Tama 3 , and Slavica Jonic 1 1 IMPMC, Sorbonne Universités - CNRS UMR 7590, UPMC Univ Paris 6, MNHN, IRD UMR 206, 75005 Paris, France . 2 Biocomputing Unit, Centro Nacional de Biotecnología – CSIC, 28049 Madrid, Spain. 3 RIKEN, Advanced Institute for Computational Sciences, Kobe, Hyogo, 650-0047, Japan.
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Elastic Image Registration To Fully Explore Macromolecular Dynamics By Electron Microscopy Qiyu Jin 1, Carlos Oscar Sanchez Sorzano 2, Isabelle Callebaut.
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Elastic Image Registration To Fully Explore Macromolecular Dynamics By Electron Microscopy
Qiyu Jin 1, Carlos Oscar Sanchez Sorzano 2, Isabelle Callebaut 1, Florence Tama 3, and Slavica Jonic 1
1 IMPMC, Sorbonne Universités - CNRS UMR 7590, UPMC Univ Paris 6, MNHN, IRD UMR 206, 75005 Paris, France. 2 Biocomputing Unit, Centro Nacional de Biotecnología – CSIC, 28049 Madrid, Spain.
3 RIKEN, Advanced Institute for Computational Sciences, Kobe, Hyogo, 650-0047, Japan.
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Normal mode analysis (NMA)
High frequenciesLow frequencies
Dynamics is described as a linear combination of independent harmonic oscillators
Mode 28 Mode 80 Mode 107
Tomato Bushy Stunt Virus (TBSV)
Deformation (displacement) amplitude :
N atoms, 3N coordinates : Nn 3,...,1
Initialstructure
Mlaaa Nllll ,...,1,,...,, 321 aModes :
Frequency : llq
3
0
022
21
L
Eigenvalues problem
Hessian: 2nd derivative of the potential
Eigenvector = normal mode Eigenvalue = frequency^2
21 aaA
Size of the system (3Nx3N)
LHAAt
ji
p
rr
E2H
Harmonic dynamics of the potential energy function around a minimum energy conformation
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, ,, 2a b a b a b
CE r r r r
E p E ra,rb ra,b
0 Rc
Elastic Network Model : Atoms connected via elastic springs
Computation of normal modes
Cowpea chlorotic mottle virus (CCMV)
Tama et al., 2002, JMB 318
TBSV
Flexible fitting: Flexible 3D-to-3D alignment of two different conformations
Study of conformational changes for unveiling biological functions:Use of normal modes to explore different conformations
A
B
C
5TBSV experiments: pseudo-atomic structure as reference
Flexible 2D-to-3D alignment
Hybrid Electron Microscopy Normal Mode Analysis (HEMNMA)Structure 22:496-506 , 2014
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• Normal modes are used within a flexible 2D-to-3D alignment of images with a reference EM or atomic structure
• Hybrid approach
• Possible movements of unknown amplitudes are determined by NMA
• Movements computed by NMA are verified experimentally by determining their
amplitudes through image analysis (flexible 2D-to-3D alignment)
• HEMNMA allows identifying intermediate conformations and continuous conformational changes of complexes in the sample
• Each particle image may represent a unique conformation
• Image classification and 3D reconstruction are not mandatory but can be done after image analysis