SPECTRAL-SAR Approach

In general, one should distinguish between two main directions in which a QSAR study may be conducted, namely the present discussion follows (Putz Duda , 2013b)  

one faces with the true challenge, namely how to extract from a single or from a eollection of QSAR models the first causes of a 

QSAR model (in turn presumed to be the closest in the QSAR pool of models to the real/recorded activity). This approach, consecrated as Spectral-SAR (Putz Lacram 2007 Putz Putz, 2011 Lacimna et al., 2007 Putz et al., 2007, 2010), provides ihe mechanistic interpretation of biological action in terms of the hierarchy of structural causes (descriptors) along the least computed path across available QSAR models  

This mechanism may be further used in a subsequent stage when extensive validation and drug design studies to recognize the molecular shape and structure (Putz et al., 2008a) which best accords with a particular mechanism of action can be envisaged. 

For this point one considers the working molecules under the actually considered most likely form producing the considered end-point, namely the anti-HIV activity produced by uracil based pyrimidines (Maruyama et al., 2003 Chemical Identifier Resolver beta 4, 2013), along two forms of their SMILES structure, as presented in Table 3.46 (Putz Duda , 2013b)  

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Nevertheless, we should note at this point that while a certain model does not satisfy the correlation factor criteria for being validated, i.e., r > 0.84, as is the case of the model la) when only hydrophobicity is taken into account, this does not mean that the descriptor or chemical domain is less relevant it is merely an indication that this descriptor may be further considered in a multivariate combination with others until produce better model. Indeed, both within standard QSAR and SPECTRAL-SAR approaches all models except la) are characterized by relevant statistics (Putz Lacrama, 2007). 

There results that the present SPECTRAL-SAR approach gives these new possibilities of hierarchically modeling of activities, over-passing the statistical analysis limited to single choices. Nevertheless, further work has to be performed by employing SPECTRAL-SAR method and of its minimal spectral path principle on many species and class of compounds in order to better validate the present results and algorithm. 

In another approach, with an aim to offer a realistic motive towards handling millions of databases and hundreds of descriptors for a fruitful structure-activity relationship (SAR), Putz and coworkers have proposed a unique QSAR model called spectral-SAR (S-SAR) [220], which considers the spectral norm in quantifying toxicity and reactivity with molecular structure. A handful of applications of the S-SAR algorithm in dealing with ecotoxicity, enzyme activity, and anticancer bioactivity are well established [221-227]. The S-SAR model coupled with Element Specific Influence Parameter (ESIP) formulations [228] are also utilized for predicting ecotoxicity measures. QSAR studies on the anti-HIV-1 activity of HEPT (l-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine) [229] and further studies involving the minimum topological difference (MTD) method [230, 231] are also reported [232]. 

However, although different from the mathematical procedure, both standard- and spectral-SAR give similar results due to the theorem that states that (Fadeeva, 1959) if the matrix X, as that from (2.91), with dimension Ny-(M+ ), N>M+, has linear independent columns, i.e., they are orthogonal as in the spectral approach, then there exists an unique matrix Q of dimension N x-(M+ ) with orthogonal columns and a triangular matrix [R] of dimension (M+ ) x-(M+ ) with the elements of the... 

The actual approach complements the SPECTRAL-SAR QSAR modeling through employing the N-dimensional chemical space of as such chemical compounds analyzed by M-descriptors in a quantum superposition (vectorial) problem, or the so-called qSAR the results are quite general and requires the inherent statistical working condition N M at least at the analytieal level the obtained diagonal-spectral... 

Within this context, the present QSAR-Spectra-SAR (QSAR-SSAR) approach responds to these OECD-QSAR principles by the present Spectral-SAR ecotoxicological principles realization, the present discussion mainly follows (Putz et al., 2011a), with special reference to projective systems/ionic liquids (Principle 3) ... 

Is this the context in which the book of Mihai V. Putz, Quantum Structure-Activity Relationship Qu-SAR) add a plus-value and insight in QSAR methodology, especially in establishing the chemical-biological mechanism of interaction, so fulfilling the celebrated fifth amendment of the OECD-QSAR directives, otherwise very difficult to assess in general as based on a multivariate equation. To this aim, new theoretical approaches, like Spectral-SAR, propose purely algebraic alternatives... 

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