TY - CHAP
T1 - Design of drugs by filtering through ADMET, physicochemical and ligand-target flexibility properties
AU - Martínez-Archundia, Marlet
AU - Bello, Martiniano
AU - Correa-Basurto, Jose
N1 - Publisher Copyright:
© Springer Science+Business Media, LLC, part of Springer Nature 2018.
PY - 2018
Y1 - 2018
N2 - There is a synergistic interaction between medicinal chemistry, chemoinformatics, and bioinformatics. The last one includes analyses of sequences as well as structural analysis which employ computational techniques such as docking studies and molecular dynamics (MD) simulations. Over the last years these techniques have allowed the development of new accurate computational tools for drug design. As a result, there have been an increased number of publications where computational methods such as pharmacophore modeling, de novo drug design, evaluation of physicochemical properties, and analysis of ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties have been quite useful for eliminating the compounds with poor physicochemical or toxicological properties. Furthermore, using MD simulations and docking analysis, it is possible to estimate the binding energy of the protein-ligand complexes by using scoring functions, as well as to structurally depict the binding pose of the compounds on proteins, in order to select the best evaluated compounds for subsequent synthetizing and evaluation through biological assays. In this work, we describe some computational tools that have been used for structure-based drug design of new compounds that target histone deacetylases (HDACs), which are known to be potential targets in cancer and parasitic diseases.
AB - There is a synergistic interaction between medicinal chemistry, chemoinformatics, and bioinformatics. The last one includes analyses of sequences as well as structural analysis which employ computational techniques such as docking studies and molecular dynamics (MD) simulations. Over the last years these techniques have allowed the development of new accurate computational tools for drug design. As a result, there have been an increased number of publications where computational methods such as pharmacophore modeling, de novo drug design, evaluation of physicochemical properties, and analysis of ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties have been quite useful for eliminating the compounds with poor physicochemical or toxicological properties. Furthermore, using MD simulations and docking analysis, it is possible to estimate the binding energy of the protein-ligand complexes by using scoring functions, as well as to structurally depict the binding pose of the compounds on proteins, in order to select the best evaluated compounds for subsequent synthetizing and evaluation through biological assays. In this work, we describe some computational tools that have been used for structure-based drug design of new compounds that target histone deacetylases (HDACs), which are known to be potential targets in cancer and parasitic diseases.
KW - ADMET properties
KW - Docking analysis
KW - Histone deacetylases
KW - Molecular dynamics simulations
KW - Pharmacophore modeling
KW - Rational drug design
UR - http://www.scopus.com/inward/record.url?scp=85051235338&partnerID=8YFLogxK
U2 - 10.1007/978-1-4939-8630-9_24
DO - 10.1007/978-1-4939-8630-9_24
M3 - Capítulo
C2 - 30039421
AN - SCOPUS:85051235338
T3 - Methods in Molecular Biology
SP - 403
EP - 416
BT - Methods in Molecular Biology
PB - Humana Press Inc.
ER -