TY - JOUR
T1 - Packing of transmembrane helices in bacteriorhodopsin folding
T2 - Structure and thermodynamics
AU - Chen, C. C.
AU - Wei, C. C.
AU - Sun, Y. C.
AU - Chen, C. M.
N1 - Funding Information:
The authors thank Dr. Tajkhorshid for providing the partial charge force field parameters for the retinal. This work is supported by the National Science Council of Taiwan under Grant No. NSC 96-2112-M-003-002. Y.-C. Sun acknowledges the partial support by the National Science Council of Taiwan under Grant No. NSC 93-2113-M-003-014. The authors thank the computer center at College of Science of NTNU and the NCHC for providing partial CPU time for the MD simulations.
PY - 2008/5
Y1 - 2008/5
N2 - We propose a coarse-grained (CG) model to study the native structure and physical properties of helical membrane proteins (HMPs) using off-lattice computer simulations. Instead of considering sequence heterogeneity explicitly, we model its effect on the packing of helices by employing a mean packing parameter r0, which is calculated from an all-atom (AA) model. Specifically, this CG model is applied to investigate the packing of helices in bacteriorhodopsin (BR), and predicts the seven helix bundle structure of BR with a root mean square deviation (RMSD) in coordinates of helix backbone atoms (N, C, Cα) of 3.99 Å from its crystal structure. This predicted structure is further refined in an AA model by Amber and the refined structure has a RMSD (in coordinates of helix backbone atoms) of 2.64 Å. The predicted packing position, tilting angle, and orientation angle of each helix in the refined structure are consistent with experimental data and their physical origins can be well understood in our model. Our results show that a reasonably good structure of BR can be predicted by using such a dual-scale approach, provided that its secondary structure is known. Starting from a random initial configuration, the folded structure can be obtained in days using a regular desktop computer. Various thermodynamic properties of helix packing of BR are also investigated in this CG model.
AB - We propose a coarse-grained (CG) model to study the native structure and physical properties of helical membrane proteins (HMPs) using off-lattice computer simulations. Instead of considering sequence heterogeneity explicitly, we model its effect on the packing of helices by employing a mean packing parameter r0, which is calculated from an all-atom (AA) model. Specifically, this CG model is applied to investigate the packing of helices in bacteriorhodopsin (BR), and predicts the seven helix bundle structure of BR with a root mean square deviation (RMSD) in coordinates of helix backbone atoms (N, C, Cα) of 3.99 Å from its crystal structure. This predicted structure is further refined in an AA model by Amber and the refined structure has a RMSD (in coordinates of helix backbone atoms) of 2.64 Å. The predicted packing position, tilting angle, and orientation angle of each helix in the refined structure are consistent with experimental data and their physical origins can be well understood in our model. Our results show that a reasonably good structure of BR can be predicted by using such a dual-scale approach, provided that its secondary structure is known. Starting from a random initial configuration, the folded structure can be obtained in days using a regular desktop computer. Various thermodynamic properties of helix packing of BR are also investigated in this CG model.
KW - Coarse-grained model
KW - Molecular dynamics simulations
KW - Monte-Carlo simulations
KW - Structure prediction
KW - Thermodynamics
KW - Transmembrane helix packing
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U2 - 10.1016/j.jsb.2008.01.003
DO - 10.1016/j.jsb.2008.01.003
M3 - Article
C2 - 18262435
AN - SCOPUS:42649115134
SN - 1047-8477
VL - 162
SP - 237
EP - 247
JO - Journal of Structural Biology
JF - Journal of Structural Biology
IS - 2
ER -