Keywords Single-particle cryo-EM Á Drug development Á Pharmacological targets
Structural biology Á High resolution
Abbreviations
3D
Three Dimension
CTF
Contrast Transfer Function
cryo-EM
Cryo-electron microscopy
CC
Cross-Correlation
DDD or DED Direct Detection Device or Direct Electron Detector
ET
Electron Tomography
EMDB
Electron Microscopy Data Bank
EM
Electron Microscopy
FEG
Field Emission Gun
FSC
Fourier Shell Correlation
MSA
Multivariate Statistical Analysis
PDB
Protein Data Bank
PCA
Principle Component Analysis
SBDD
Structure-Based Drug Design
SNR
Signal-to-Noise Ratio
SSNR
Spectral SNR
TEM
Transmission Electron Microscopy
1 Introduction
The importance of structural biology in understanding the principles of molecular
function of proteins, the workforce of cellular world, underpins its use in health
science and pharma industries. Classically, protein crystallography was ruling the
world of structure-based drug design (SBDD). This was mainly due to the capability of protein crystallography to solve high (better than 1.8 Å), atomic (better
than 1.2 Å), and ultra-high (better than 0.95 Å)-resolution 3D structures, which
give information of protein drug molecular interaction at various levels.
Particularly, the positions of hydrogen atoms were located in many atomic and
ultra-high-resolution protein structures. There were no other methods that could
rival the versatility of obtaining 3D atomic-level macromolecular structures with
which crystallography could achieve. Of the 131,108 protein structures in PDB (as
on June 15, 2018), 90% of structures among them were solved by X-ray crystallography technique and 8% by NMR technique. The remaining 2% of structures by
large were solved by electron microscopy, electron crystallography, hybrid, and
other methods, which include neutron diffraction, solution scattering, fiber
diffraction. Clearly, the PDB data suggests that the protein crystallography technique dominates till date. However, the protein crystallography method comes with
376
R. Natesh
Structural biology Á High resolution
Abbreviations
3D
Three Dimension
CTF
Contrast Transfer Function
cryo-EM
Cryo-electron microscopy
CC
Cross-Correlation
DDD or DED Direct Detection Device or Direct Electron Detector
ET
Electron Tomography
EMDB
Electron Microscopy Data Bank
EM
Electron Microscopy
FEG
Field Emission Gun
FSC
Fourier Shell Correlation
MSA
Multivariate Statistical Analysis
PDB
Protein Data Bank
PCA
Principle Component Analysis
SBDD
Structure-Based Drug Design
SNR
Signal-to-Noise Ratio
SSNR
Spectral SNR
TEM
Transmission Electron Microscopy
1 Introduction
The importance of structural biology in understanding the principles of molecular
function of proteins, the workforce of cellular world, underpins its use in health
science and pharma industries. Classically, protein crystallography was ruling the
world of structure-based drug design (SBDD). This was mainly due to the capability of protein crystallography to solve high (better than 1.8 Å), atomic (better
than 1.2 Å), and ultra-high (better than 0.95 Å)-resolution 3D structures, which
give information of protein drug molecular interaction at various levels.
Particularly, the positions of hydrogen atoms were located in many atomic and
ultra-high-resolution protein structures. There were no other methods that could
rival the versatility of obtaining 3D atomic-level macromolecular structures with
which crystallography could achieve. Of the 131,108 protein structures in PDB (as
on June 15, 2018), 90% of structures among them were solved by X-ray crystallography technique and 8% by NMR technique. The remaining 2% of structures by
large were solved by electron microscopy, electron crystallography, hybrid, and
other methods, which include neutron diffraction, solution scattering, fiber
diffraction. Clearly, the PDB data suggests that the protein crystallography technique dominates till date. However, the protein crystallography method comes with
376
R. Natesh