Abstract
The quasi-docking procedure with a combination of the classical MMFF94 force field and the PM7 quantum-chemical semiempirical method is applied for docking ligands into proteins with which they are co-crystallized. Main peculiarities of the test set of protein-ligand complexes are: a high resolution of the structures obtained from Protein Data Bank, no missed residues or atoms in the active sites of the proteins and the availability of experimentally measured protein-ligand binding free energies including separate contributions of the enthalpy and entropy terms. The goal of this work is to determine positioning accuracy of the quasi-docking by a comparison of best docked ligand poses with the respective ligand poses in the crystallized protein-ligand complexes, to estimate values of the protein-ligand binding enthalpy for the best ligand poses and to compare these values with the measured ones. The best ligand pose corresponds to the global energy minimum of the protein-ligand complex calculated with PM7 and with the COSMO continuum solvent model either in the old parameterization, COSMO, or in the recent one, COSMO2, in the quasi-docking procedure. It is found that the docking positioning accuracy is better in the case of PM7 with COSMO energy calculations than with COSMO2 calculations. The correlation between values of the calculated and experimentally measured binding enthalpy is also better, R = 0.74, for the PM7+COSMO energy.
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Acknowledgements
The work was financially supported by the Russian Science Foundation, Agreement no. 15-11-00025-П. The research is carried out using the equipment of the shared research facilities of HPC computing resources at Lomonosov Moscow State University, including the Lomonosov supercomputer [23].
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Sulimov, A., Kutov, D., Gribkova, A., Ilin, I., Tashchilova, A., Sulimov, V. (2019). Search for Approaches to Supercomputer Quantum-Chemical Docking. In: Voevodin, V., Sobolev, S. (eds) Supercomputing. RuSCDays 2019. Communications in Computer and Information Science, vol 1129. Springer, Cham. https://doi.org/10.1007/978-3-030-36592-9_30
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