Proteins QSAR models

The HlV-1 protease is responsible for processing the protein precursors to the enzymes (integrase, protease and reverse transcriptase) and the structural proteins of the HIV-1 virus. Maw and Hall found that topological indices provide rehable QSAR models for the IC50 data of 32 HIV-1 protease inhibitors [29]. The best QSAR model, with r = 0.86, s=0.60 and q = 0.79, was obtained with the shape index Ka, the connechvity index the sum of HE-state indices for ah groups that act as... 

Hall, L. M Hall, L H Kier, L B. QSAR modeling of 3-lactam binding to human serum proteins. /. Comput.-Aided Mol. Des. 2003, 17,103-118. 

Poor intestinal absorption of a potential drug molecule can be related to poor physicochemical properties and/or poor membrane permeation. Poor membrane permeation could be due to low paracellular or transcellular permeability or the net result of efflux from transporter proteins including MDRl (P-gp) or MRP proteins situated in the intestinal membrane. Cell lines with only one single efflux transporter are currently engineered for in vitro permeability assays to get suitable data for reliable QSAR models. In addition, efforts to gain deeper insight into P-gp and ABC on a structural basis are going on [131, 132]. 

The underlying theory of Quantitative Structure-Activity Relationship (QSAR) is that biological activity is directly related to molecular structure. Therefore, molecules with similar structure will possess similar bioactivities for similar proteins/receptors/enzymes and the changes in structure will be represented through the changes in the bioactivities. The best general description of a QSAR model is... 

LOO cross-validation analysis of F-W QSAR models showed an overall agreement between predicted and experimental pICso for each individual combination of chemical series and protein target. 

L.B. Kier, L.M. Hall and L.H. Hall, QSAR Modeling of Drug Binding to Protein, MDL-Whitepaper, 2002. 

Insight II Program with modules for homology modeling, protein structure analysis, pharmacophore/3D-QSAR modeling, MD www.accelrys.com/insight/Insight2.html... 

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