On Two Novel Parameters for Validation of Predictive QSAR Models 英文参考文献.docVIP

Molecules 2009, 14, 1660-1701; doi:10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article On Two Novel Parameters for Validation of Predictive QSAR Models Partha Pratim Roy, Somnath Paul, Indrani Mitra and Kunal Roy * Drug Theoretics and Cheminformatics Lab, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India; E-mails: partha_chemju@yahoo.co.in (P-P.R.), somnath_juph@yahoo.co.in (S.P.), indranimitra06@ (I.M.) * Author to whom correspondence should be addressed; E-mail: kunalroy_in@ or kroy@pharma.jdvu.ac.in; Fax: +91-33-2837 1078. Received: 16 April 2009 in revised form: 24 April 2009 / Accepted: 28 April 2009 / Published: 29 April 2009 Abstract: Validation is a crucial aspect of quantitative structure–activity relationship (QSAR) modeling. The present paper shows that traditionally used validation parameters (leave-one-out Q2 for internal validation and predictive R2 for external validation) may be supplemented with two novel parameters rm2 and Rp2 for a stricter test of validation. The parameter rm2(overall) penalizes a model for large differences between observed and predicted values of the compounds of the whole set (considering both training and test sets) while the parameter Rp2 penalizes model R2 for large differences between determination coefficient of nonrandom model and square of mean correlation coefficient of random models in case of a randomization test. Two other variants of rm2 parameter, rm2(LOO) and rm2(test), penalize a model more strictly than Q2 and R2pred respectively. Three different data sets of moderate to large size have been used to develop multiple models in order to indicate the suitability of the novel parameters in QSAR studies. The results show that in many cases the developed models could satisfy the requirements of conventional parameters (Q2 and R2pred) but fail to achieve th