Supercomputer Docking: Investigation of Low Energy Minima of Protein-Ligand Complexes

Danil C. Kutov, Alexey V. Sulimov, Vladimir B. Sulimov

Abstract


It is shown that the global energy minimum of a protein-ligand complex, when the energy is calculated by the PM7 quantum-chemical semiempirical method with the COSMO implicit solvent model, can be determined as follows. First, the low energy minima are found by a docking program when the protein-ligand energy is calculated with the MMFF94 force field in vacuum. Second, energies of all these minima are recalculated with the PM7 method and the COSMO implicit solvent model. Third, among these recalculated energies the minimal energy is determined and the respective minimum is the global energy minimum when the energy is calculated with the PM7 method and the COSMO implicit solvent model. The optimal width of the spectrum of low energy minima found with MMFF94 in vacuum is determined to perform minimal quantity of quantum-chemical recalculations. The proposed approach allows to perform docking in solvent with the quantum-chemical method and to increase the docking positioning accuracy.


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References


Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., Bourne, P.E.: The protein data bank. Nucleic Acids Research 28(1), 235–242 (2000), DOI: 10.1093/nar/28.1.235

Halgren, T.A.: Merck molecular force field. Journal of Computational Chemistry 17(5-6), 490–519 (1996), DOI: 10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-P

Klamt, A., Schuurmann, G.: COSMO: a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. J. Chem. Soc-Perkin Trans. 2 (5), 799–805 (1993), DOI: 10.1039/P29930000799

Oferkin, I.V., Katkova, E.V., Sulimov, A.V., Kutov, D.C., Sobolev, S.I., Voevodin, V.V., Sulimov, V.B.: Evaluation of Docking Target Functions by the Comprehensive Investigation of Protein-ligand Energy Minima. Adv Bioinformatics 2015, 126858 (2015)

Sadovnichy, V., Tikhonravov, A., Voevodin, V., Opanasenko, V.: ”Lomonosov”: Supercomputing at Moscow State University. In: Contemporary High Performance Computing: From Petascale toward Exascale. pp. 283–307. Chapman & Hall/CRC Computational Science, CRC Press, Boca Raton, United States (2013)

Stewart, J.J.: MOPAC2016. http://OpenMOPAC.net (2016), accessed: 2018-09-06

Stewart, J.: Optimization of parameters for semiempirical methods VI: More modifications to the NDDO approximations and re-optimization of parameters. J. Mol. Model. 19(1), 1–32 (2013), DOI: 10.1007/s00894-012-1667-x

Sulimov, A.V., Kutov, D.C., Katkova, E.V., Ilin, I.S., Sulimov, V.B.: New generation of docking programs: Supercomputer validation of force fields and quantum-chemical methods for docking. J. Mol. Graph. Model. 78, 139–147 (2017), DOI: 10.1016/j.jmgm.2017.10.007

Sulimov, A.V., Zheltkov, D.A., Oferkin, I.V., Kutov, D.C., Katkova, E.V., Tyrtyshnikov, E.E., Sulimov, V.B.: Evaluation of the novel algorithm of flexible ligand docking with moveable target-protein atoms. Comput. Struct. Biotechnol. J. 15, 275–285 (2017), DOI: 10.1016/j.csbj.2017.02.004

Sulimov, V.B., Mikhalev, A.Y., Oferkin, I.V., Oseledets, I.V., Sulimov, A.V., Kutov, D.C., Katkova, E.V., Tyrtyshnikov, E.E.: Polarized continuum solvent model: Considerable acceleration with the multicharge matrix approximation. Int. J. Appl. Eng. Res. 10(24), 44815–44830 (2015)




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