[The model of prediction of the inhibition of neuraminidases of influenza A and B based on a reduced set of energy terms]
- PMID: 31876523
- DOI: 10.18097/PBMC20196506520
[The model of prediction of the inhibition of neuraminidases of influenza A and B based on a reduced set of energy terms]
Abstract
The overall model for prediction of IC50 values for inhibitors of neuraminidase influenza virus A and B has been created. It combines data about IC50 values of complexes of 40 variants of neuraminidases of influenza A (7 serotypes) and B and three known inhibitors (oseltamivir, zanamivir, peramivir). The model also uses only data of enthalpy contributions to the potential energy of inhibitor/protein and substrate (MUNANA)/protein complexes. The calculation procedures are ported to use software with support of GPU accelerators, that significant decrease the computation time. The corresponding correlation coefficient (R²) for pIC50 prediction was within 0.45-0.58, the SEM values of around 0.7 (the range of used pIC50 data set is from 4.55 to 10.22).
Poluchena obshchaia model' predskazaniia velichiny IC50 (kontsentratsii, vyzyvaiushcheĭ 50% tormozhenie aktivnosti fermenta), ob"ediniaiushchaia dannye dlia 40 variantov neĭraminidaz virusov grippa A (7 serotipov) i B i trekh izvestnykh ingibitorov – osel'tamivira, zanamivira, peramivira – i ispol'zuiushchaia dannye tol'ko ob éntal'piĭnykh vkladakh v potentsial'nuiu énergiiu kompleksov ingibitor/belok i substrat/belok (MUNANA). Raschety adaptirovany dlia ispol'zovaniia programmnogo obespecheniia s podderzhkoĭ graficheskikh uskoriteleĭ, sokrashchaiushchego vremia vychisleniĭ. Znacheniia R² dlia predskazaniia velichin pIC50 dlia testovykh vyborok lezhat v predelakh 0,45-0,58, znachenie sredneĭ oshibki – 0,7 (pri diapazone obuchaiushcheĭ vyborki pIC50 ot 4,55 do 10,22).
Keywords: QSAR; computational methods; influenza virus neuraminidase; inhibitors.