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Use of the Monte Carlo Method for OECD Principles‐Guided QSAR Modeling of SIRT1 Inhibitors
Author(s) -
Kumar Ashwani,
Chauhan Shilpi
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201600268
Subject(s) - quantitative structure–activity relationship , monte carlo method , test set , set (abstract data type) , computational biology , computer science , notation , human immunodeficiency virus (hiv) , biological system , chemistry , mathematics , artificial intelligence , machine learning , statistics , biology , arithmetic , immunology , programming language
SIRT1 inhibitors offer therapeutic potential for the treatment of a number of diseases including cancer and human immunodeficiency virus infection. A diverse series of 45 compounds with reported SIRT1 inhibitory activity has been employed for the development of quantitative structure–activity relationship (QSAR) models using the Monte Carlo optimization method. This method makes use of simplified molecular input line entry system notation of the molecular structure. The QSAR models were built up according to OECD principles. Three subsets of three splits were examined and validated by respective external sets. All the three described models have good statistical quality. The best model has the following statistical characteristics: R 2 = 0.8350, Q 2 test = 0.7491 for the test set and R 2 = 0.9655, Q 2 ext = 0.9261 for the validation set. In the mechanistic interpretation, structural attributes responsible for the endpoint increase and decrease are defined. Further, the design of some prospective SIRT1 inhibitors is also presented on the basis of these structural attributes.