Publication: Improved prediction of HIV-1 protease-inhibitor binding energies by molecular dynamics simulations
Issued Date
2003-04-01
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ISSN
14726807
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2-s2.0-3042668215
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Mahidol University
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SCOPUS
Bibliographic Citation
BMC Structural Biology. Vol.3, (2003), 1-9
Suggested Citation
Ekachai Jenwitheesuk, Ram Samudrala Improved prediction of HIV-1 protease-inhibitor binding energies by molecular dynamics simulations. BMC Structural Biology. Vol.3, (2003), 1-9. doi:10.1186/1472-6807-3-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/20747
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Title
Improved prediction of HIV-1 protease-inhibitor binding energies by molecular dynamics simulations
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Abstract
Background: The accurate prediction of enzyme-substrate interaction energies is one of the major challenges in computational biology. This study describes the improvement of protein-ligand binding energy prediction by incorporating protein flexibility through the use of molecular dynamics (MD) simulations. Results: Docking experiments were undertaken using the program AutoDock for twenty-five HIV-1 protease-inhibitor complexes determined by x-ray crystallography. Protein-rigid docking without any dynamics produced a low correlation of 0.38 between the experimental and calculated binding energies. Correlations improved significantly for all time scales of MD simulations of the receptor-ligand complex. The highest correlation coefficient of 0.87 between the experimental and calculated energies was obtained after 0.1 picoseconds of dynamics simulation. Conclusion: Our results indicate that relaxation of protein complexes by MD simulation is useful and necessary to obtain binding energies that are representative of the experimentally determined values.