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| Multi-resolution and Multi-length Scale Simulation of Supermolecular Complexes |
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Large-scale
conformational transitions in protein structures play an important role in a
variety of cellular processes. Understanding such transitions is one of the
central tasks of modern biophysics and structural biology. Among all the
available structural and biophysical methods, computer simulation is a powerful
method that allows one to model the motions of proteins in atomic details.
The
research projects primarily focus on systems that involve coordinated large
domain movements. Our recent work on the molecular chaperonin GroEL and F1-ATPase
provided paradigms for this type of research, and it also demonstrates that
molecular dynamics simulation has come into an age of realistically modeling
very large protein complexes.
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| Structural Refinement for X-ray, cryo-EM and Fiber Diffraction |
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In
recent history, molecular dynamics simulation has been successfully employed to
significantly improve the structure refinement in X-ray crystallography.
However, as structural biology moves towards meeting the new challenges imposed
by the study of more complex and more dynamic biological systems, more advanced
computational methods are urgently needed to effectively deal with molecular
motions in structure refinement.
Our group is committed to improving structure refinement in X-ray
crystallography, electron cryomicroscopy (cryo-EM) and fiber diffraction.
Quantized elastic deformational model (QEDM)
has been demonstrated highly effective in assisting cryo-EM single-particle
reconstruction of intrinsically flexible biological systems. Substructure
synthesis method (SSM)
is extremely powerful for enhancing the structure refinement against fiber
diffraction data. Moreover, important progress of improving X-ray structure
refinement has been recently achieved. These lines of research will undoubtedly
provide powerful tools for structure refinement in the wider fields of
structural biology.
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| Structure Modeling and Prediction |
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With the advance of cryo-EM single-particle
reconstruction, more and more intermediate-resolution structures are available.
It would be extremely useful if protein secondary structures and protein
topology can be determined from intermediate-resolution data.
Our group has recently developed
sheetminer
and sheettracer that are capable of accurately locating
beta-sheets and
building beta-strands in intermediate-resolution density maps. Once protein
secondary structures are in place, protein topology can be determined using
approaches developed in our group. These methods will greatly enhance one's
ability to obtain meaningful information about protein structure and function
from intermediate-resolution data.
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