QSAR without arbitrary descriptors: The electron-conformational method

COMP 59

Isaac B Bersuker, bersuker@cm.utexas.edu, Department of Chemistry & Biochemistry, Institute for Theoretical Chemistry, The University of Texas at Austin, 1 University Station A5300, Austin, TX 78712
It is shown that the electronic structure and geometry of the molecular system obtained from conformational analysis and quantum-chemical calculations and presented in a matrix form serves as a unique, most accurate descriptor in its interaction with the bioreceptor instead of arbitrary descriptors in conventional QSAR methods. By processing such electron-conformational (EC) matrices of a set of molecules in relation to their known activities in comparison with EC of inactive compounds by means of special programs, a common submatrix of activity is revealed, the pharmacophore (Pha). The latter is thus unique with a theoretically 100% qualitative (yes, no) prediction of the activity. The second part of the EC method takes into account the influence of Pha flexibility and the out-of-Pha groups on the activity quantitatively by means of regression analysis. Specific calculations are presented for antimitotic antitumor activity, glutamate receptor agonists, and antidiabetics.