A universal model of inhibition of neuraminidases from various influenza virus strains by a particular has been developed. It is based on known 3D data for neuraminidases from three influenza virus strains (A/Tokyo/3/67, A/tern/Australia/G70C/75, B/Lee/40) and modeling of 3D structure of neuraminidases from other strains (A/PR/8/34 è A/Aichi/2/68). Using docking and molecular dynamics, we have modeled 235 enzyme-ligand complexes for 89 compounds with known IC50 values. Selection of final variants among three results obtained for each enzyme-ligand pair and calculation of independent variables for generation of linear regression equations was performed using MM-PBSA/MM-GBSA. This resulted in the set of equations individual strains and the equations pooling all the data. Thus using this approach it is possible to predict inhibition for neuraminidase from each the considered strains by a particular inhibitor and to predict the range of its action on neuraminidases from various influenza virus strains.
Sozdana universal'naia model' predskazaniia tormozheniia neĭraminidazy razlichnykh shtammakh virusa grippa zadannym ingibitorom. Ona osnovana na izvestnykh dannykh o trekhmernoĭ strukture (3D) neĭraminidazy iz razlichnykh shtammov virusa grippa (A/Tokyo/3/67, A/tern/Australia/G70C/75, B/Lee/40), a takzhe modelirovanii trekhmernoĭ struktury neĭraminidazy drugikh shtammov (A/PR/8/34 i A/Aichi/2/68). S ispol'zovaniem dokinga i molekuliarnoĭ dinamiki byli smodelirovany 235 kompleksov dlia ligandov s izvestnymi znacheniiami IC50 dlia 186 soedineniĭ. Otbor konechnykh variantov iz trekh promezhutochnykh dlia kazhdoĭ pary belok/ligand i raschet nezavisimykh peremennykh dlia postroeniia uravneniĭ lineĭnoĭ regressii vypolnen s ispol'zovaniem MM-PBSA/MM-GBSA. V rezul'tate byl poluchen nabor uravneniĭ, kak dlia otdel'nykh shtammov, tak i uravnenie, ob"ediniaiushchee vse dannye. Takim obrazom, rezul'taty dannoĭ raboty pokazyvaiut real'nuiu vozmozhnost' predskazaniia stepeni ingibirovaniia neĭraminidazy dlia kazhdogo iz rassmotrennykh shtammov proizvol'nym ingibitorom i predskazat' spektr ego deĭstviia na razlichnye varianty virusa grippa.
Keywords: QSAR; computational methods; influenza virus neuraminidase; inhibitors.