Combining fragment homology modeling with molecular dynamics aims at prediction of Ca²⁺ binding sites in CaBPs.
The family of calcium-binding proteins (CaBPs) consists of dozens of members and contributes to all aspects of the cell's function, from homeostasis to learning and memory. However, the Ca²⁺-binding mechanism is still unclear for most of CaBPs. To identify the Ca²⁺-binding sites of CaBPs, this study presented a computational approach which combined the fragment homology modeling with molecular dynamics simulation. For validation, we performed a two-step strategy as follows: first, the approach is used to identify the Ca²⁺-binding sites of CaBPs, which have the EF-hand Ca²⁺-binding site and the detailed binding mechanism. To accomplish this, eighteen crystal structures of CaBPs with 49 Ca²⁺-binding sites are selected to be analyzed including calmodulin. The computational method identified 43 from 49 Ca²⁺-binding sites. Second, we performed the approach to large-conductance Ca²⁺-activated K⁺ (BK) channels which don't have clear Ca²⁺-binding mechanism. The simulated results are consistent with the experimental data. The computational approach may shed some light on the identification of Ca²⁺-binding sites in CaBPs.
Institute of Biophysics, Hebei University of Technology, Tianjin, China.
ChunLi
C
Pang
TianGuang
T
Cao
JunWei
J
Li
MengWen
M
Jia
SuHua
S
Zhang
ShuXi
S
Ren
HaiLong
H
An
Yong
Y
Zhan
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D064026:Calbindins / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020832:EF Hand Motifs; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats
D064026:Calbindins; D002135:Calcium-Binding Proteins; D016601:RNA-Binding Proteins; C075197:high density lipoprotein binding protein; D002118:Calcium