application of the linear interaction energy method (LIE) to estimate the binding free energy values of escherichia coli wild-type and mutant arginine repressor c-terminal domain (ARGRC)-l-arginine and argrc-l-citrulline protein-ligand complexes

• Main Authors: Asi, A.M., Rahman, N.A., Merican, Amir Feisal
• Format: Article
• Published: Elsevier 2004
• Subjects: QH301 Biology
• Online Access: http://eprints.um.edu.my/4943/; http://ac.els-cdn.com/S1093326303001748/1-s2.0-S1093326303001748-main.pdf?_tid=f48b09ee-2e02-11e2-b396-00000aab0f27&acdnat=1352860280_6e8c1452757e9f9add3dc0f153250bef

Protein-ligand binding free energy values of wild-type and mutant C-terminal domain of Escherichia coli arginine repressor (ArgRc) protein systems bound to L-arginine or L-citrulline molecules were calculated using the linear interaction energy (LIE) method by molecular dynamics (MD) simulation. The binding behaviour predicted by the dissociation constant (K-d) calculations from the binding free energy values showed preferences for binding Of L-arginine to the wild-type ArgRc but not to the mutant ArgRc(D128N). On the other hand, L-citrulline do not favour binding to wild-type ArgRc but prefer binding to mutant ArgRc(D128N). The dissociation constant for the wild-type ArgRc-L-arginine complex obtained in this study is in agreement with reported experimental results [J. Mol. Biol. 235 (1994) 221-230]. Our results also support the experimental data for the binding Of L-citrulline to the mutant ArgRc(D128N) [J. Mol. Biol. 279 (1998) 753-760]. These showed that LIE method for protein-ligand binding free energy calculation could be applied to the wild-type and the mutant E. coli ArgRc-L-arginine and ArgRc-L-citrulline protein-ligand complexes and possibly to other transcriptional repressor-co-repressor systems as well. (C) 2003 Elsevier Inc. All rights reserved.