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Molecular dynamics simulation of the calmodulin–trifluoperazine complex in aqueous solution
Author(s) -
Yamaotsu Noriyuki,
Suga Masaki,
Hirono Shuichi
Publication year - 2001
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/1097-0282(20010405)58:4<410::aid-bip1017>3.0.co;2-0
Subject(s) - trifluoperazine , calmodulin , chemistry , molecule , molecular dynamics , binding site , crystal structure , total factor productivity , aqueous solution , binding domain , stereochemistry , crystallography , biophysics , computational chemistry , biochemistry , enzyme , organic chemistry , biology , economics , productivity , macroeconomics
Trifluoperazine (TFP) has been widely studied in relation to its mode of binding and its inactivation of calmodulin (CaM). Most studies in solution have indicated that CaM has two high‐affinity binding sites for TFP. The crystal structure of the 1:4 CaM‐TFP complex (CaM‐4TFP) shows that three TFP molecules bind to the C‐domain of CaM, and that one TFP molecule binds to the N‐domain. In contrast, the crystal structure of the 1:1 CaM‐TFP complex (CaM‐1TFP) shows that one TFP molecule binds to the C‐domain. It has been thought that the binding of one TFP molecule to the C‐domain is followed by binding to the N‐domain. The crystal structure of the 1:2 CaM‐TFP complex (CaM‐2TFP), moreover, has recently been determined, showing that two TFP molecules bind to the C‐domain. In order to determine the structure of the CaM‐TFP complex and to clarify the interaction between CaM and TFP in solution, we performed a molecular dynamics simulation of the CaM‐TFP complex in aqueous solution starting from the CaM‐4TFP crystal structure. The obtained solution structure is very similar to the CaM‐2TFP crystal structure. The computer simulation showed that the binding ability of the secondary binding site of the C‐domain is higher than that of the primary binding site of the N‐domain. © 2001 John Wiley & Sons, Inc. Biopolymers 58: 410–421, 2001