TY - JOUR
T1 - Conformational flexibility of pyruvate dehydrogenase complexes
T2 - A computational analysis by quantized elastic deformational model
AU - Kong, Yifei
AU - Ming, Dengming
AU - Wu, Yinghao
AU - Stoops, James K.
AU - Zhou, Z. Hong
AU - Ma, Jianpeng
N1 - Funding Information:
This research was supported, in part, by grants from the American Heart Association (AHA-TX0160107Y to J.M. and 0240216N to Z.H.Z.), the Robert A. Welch Foundation (Q-1512 to J.M. and AU-1492 to Z.H.Z.), the United States Public Services (AI46420 and CA94809 to Z.H.Z.; HL42886 and EB00276 to J.K.S.; and R01-GM067801 to J.M.), National Science Foundation Career Award (no. MCB-0237796 to J.M.). Z.H.Z. is a Pew Scholar in the Biomedical Sciences. J.M. is a recipient of the Award for Distinguished Young Scholars Abroad from the National Natural Science Foundation of China.
PY - 2003/6/27
Y1 - 2003/6/27
N2 - Pyruvate dehydrogenase complex (PDC) is one of the largest multienzyme complexes known and consists of a dodecahedral E2 core to which other components are attached. We report the results of applying a new computational method, quantized elastic deformational model, to simulating the conformational fluctuations of the truncated E2 core, using low-resolution electron cryomicroscopy density maps. The motional features are well reproduced; especially, the symmetric breathing mode revealed in simulation is nearly identical with what was observed experimentally. Structural details of the motions of the trimeric building blocks, which are critical to facilitating the global expansion and contraction of the complex, were revealed. Using the low-resolution maps from electron cryomicroscopy reconstructions, the simulations showed a picture of the motional mechanism of the PDC core, which is an example without precedent of thermally activated global dynamics. Moreover, the current results support an earlier suggestion that, at low resolution and without the use of amino acid sequence and atomic coordinates, it is possible for computer simulations to provide an accurate description of protein dynamics.
AB - Pyruvate dehydrogenase complex (PDC) is one of the largest multienzyme complexes known and consists of a dodecahedral E2 core to which other components are attached. We report the results of applying a new computational method, quantized elastic deformational model, to simulating the conformational fluctuations of the truncated E2 core, using low-resolution electron cryomicroscopy density maps. The motional features are well reproduced; especially, the symmetric breathing mode revealed in simulation is nearly identical with what was observed experimentally. Structural details of the motions of the trimeric building blocks, which are critical to facilitating the global expansion and contraction of the complex, were revealed. Using the low-resolution maps from electron cryomicroscopy reconstructions, the simulations showed a picture of the motional mechanism of the PDC core, which is an example without precedent of thermally activated global dynamics. Moreover, the current results support an earlier suggestion that, at low resolution and without the use of amino acid sequence and atomic coordinates, it is possible for computer simulations to provide an accurate description of protein dynamics.
KW - Conformational flexibility
KW - Elastic deformation
KW - Elastic network
KW - Large conformational change
KW - Normal mode analysis
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U2 - 10.1016/S0022-2836(03)00555-2
DO - 10.1016/S0022-2836(03)00555-2
M3 - Article
C2 - 12818207
AN - SCOPUS:0037666985
SN - 0022-2836
VL - 330
SP - 129
EP - 135
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 1
ER -