prediction. Development of novel validation parameters for judging quality of QSAR models is also important. Application Chemical One of the first historical QSAR applications was to predict boiling points. It is well known for instance that within a particular family of chemical compounds, especially of organic chemistry, that there are strong correlations between structure and observed properties. A simple example is the relationship between the number of carbons in alkanes and their boiling points. There is a clear trend in the increase of boiling point with an increase in the number carbons, and this serves as a means for predicting the boiling points of higher alkanes. A still very interesting application is the Hammett equation, Taft equation and pKa prediction methods. Biological The biological activity of molecules is usually measured in assays to establish the level of inhibition of particular signal transduction or metabolic pathways. Drug discovery often involves the use of QSAR to identify chemical structures that could have good inhibitory effects on specific targets and have low toxicity (non-specific activity). Of special interest is the prediction of partition coefficient log P, which is an important measure used in identifying "druglikeness" according to Lipinski's Rule of Five. While many quantitative structure activity relationship analyses involve the interactions of a family of molecules with an enzyme or receptor binding site, QSAR can also be used to study the interactions between the structural domains of proteins. Protein-protein interactions can be quantitatively analyzed for structural variations resulted from site-directed mutagenesis. It is part of the machine learning method to reduce the risk for a SAR paradox, especially taking into account that only a finite amount of data is available (see also MVUE). In general, all QSAR problems can be divided into coding and learning. Applications (Q)SAR models have been used for risk management. QSARS are suggested by regulatory authorities; in the European Union, QSARs are suggested by the REACH regulation, where "REACH" abbreviates "Registration, Evaluation, Authorisation and Restriction of Chemicals". Regulatory application of QSAR methods includes in silico toxicological assessment of genotoxic impurities. Commonly used QSAR assessment software such as DEREK or CASE Ultra (MultiCASE) is used to genotoxicity of impurity according to ICH M7. The chemical descriptor space whose convex hull is generated by a particular training set of chemicals is called the training set's applicability domain. Prediction of properties of novel chemicals that are located outside the applicability domain uses