Computational chemistry in drug lead discovery and design

CAVASOTTO, CLAUDIO N.; AUCAR, MARÍA G.; ADLER, NATALIA S.

International Journal of Quantum Chemistry

John Wiley and Sonds

Año: 2019 vol. 119 p. 1 - 19

The maincontributions of our group during the last fifteen years developing and usingbiomolecular simulation tools in drug lead discovery and design, in closecollaboration with experimental researchers, are presented. Special emphasishas been given to methodological improvements in the following areas: i) targethomology modeling incorporating knowledge about known ligands to accuratelycharacterize the binding site; ii) designing alternative strategies to accountfor protein flexibility in high-throughput docking; iii) development ofstochastic- and normal-mode-based methods to de novo design structurallydiverse protein conformers; iv) development and validation of quantummechanical semi-empirical linear-scaling calculations to correctly estimateligand binding free energy. Several successful cases of computer-aided drugdiscovery are also presented, especially our recent work on viral targets.