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Improved prediction of HIV-1 protease-inhibitor binding energies by molecular dynamics simulations

✍ Scribed by Ekachai Jenwitheesuk; Ram Samudrala

Publisher
BioMed Central
Year
2003
Tongue
English
Weight
710 KB
Volume
3
Category
Article
ISSN
1472-6807

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✦ Synopsis

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.

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