Article,
A Dft Study of the Inhibition of the Papain-Like Protease (Plpro) from the Sars Coronavirus by a Group of 4-Piperidinecarboxamide Derivatives
Research Journal of Pharmaceutical Biological and Chemical Sciences, 5 (5): 12 (2014)
Abstract
We present an analysis of the relationships between the electronic structure and the SARS coronavirus papain-like protease inhibitory capacity of a series of 4-piperidinecarboxamide derivatives. The electronic structure of all the molecules was calculated within the Density Functional Theory at the B3LYP/631g(d,p) level with full geometry optimization. We found a statistically significant relationship between the variation of the inhibitory capacity and the variation of the values of local atomic reactivity indices pertaining to five atoms of a common skeleton (n=15, adj R 2 =0.91, F(5,9)=29.79 (p<0.00002), SD=0.24). Molecular electrostatic potentials and conformational aspects of the molecules are discussed. A partial inhibitory pharmacophore is proposed and discussed. This is another example of the needlessness of using hundreds or thousands of reactivity indices and descriptors to get useful physically-based information from experimental results.
