Title:In Silico Studies Most Employed in the Discovery of New Antimicrobial Agents
Volume: 23
Issue: 29
Author(s): F. Tamay-Cach, M. L. Villa-Tanaca, J. G. Trujillo-Ferrara, D. Alemán-González-Duhart, J. C. Quintana-Pérez and I. A. González-Ramírez, J. Correa-Basurto
Affiliation:
关键词:
Antimicrobial agents
摘要: The present review summarizes the methods most used in drug search
and design, which may help to keep pace with the growing antibiotic resistance
among pathogens. The rate of reduction in the effectiveness of many antimicrobial
medications, caused by this resistance, is faster than new drug
development, thereby creating a worldwide public health threat. Among the
scientific community, the urgency of finding new drugs is peaking interest in the
use of in silico studies to explore the interaction of compounds with target
receptors. With this approach, small molecules (designed or retrieved from data
bases) are tested with computer-aided molecular simulation to explore their
efficacy. That is, ligand-protein complexes are constructed and evaluated via
virtual screening (VS), molecular dynamics (MD), and docking simulations with
the data from the physical, chemical and pharmacological properties of such
molecules. Additionally, the application of quantitative structure-activity
relationship (QSAR), multi-target quantitative structure-activity relationship (mt-
QSAR), and multi-tasking quantitative structure-biological effect (mtk-QSBER)
can be enhanced by principal component analysis and systematic workflows.
These types of studies aid in selecting a group of promising molecules with high
potency and selectivity as well as low toxicity, thus making in vitro and in vivo
(animal model) testing more efficient. Since knowledge of the receptor
topography and receptor-ligand interactions has yielded promising compounds
and effective drugs, there is now no doubt that the use of in silico tools can lead to
more rapid validation of new potential drugs for preclinical studies and clinical
trials.
