RT Journal Article
T1 Optimizing ligand conformations in flexible protein targets: a multi-objective strategy
A1 Lopez-Camacho, Esteban
A1 Jesus Garcia-Godoy, Maria
A1 Garcia-Nieto, Jose
A1 Nebro, Antonio J.
A1 Aldana-Montes, Jose F.
K1 Molecular docking
K1 Multi-objective optimization
K1 Metaheuristics
K1 Hiv-1 protease
K1 Molecular docking
K1 Wild-type
K1 Inhibition
K1 Algorithm
K1 Accuracy
AB Finding the orientation of a ligand (small molecule) with the lowest binding energy to the macromolecule (receptor) is a complex optimization problem, commonly called ligand-protein docking. This problem has been usually approached by minimizing a single objective that corresponds to the final free energy of binding. In this work, we propose a new multi-objective strategy focused on minimizing: (1) the root mean square deviation (RMSD) between the co-crystallized and predicted ligand atomic coordinates, and (2) the ligand-receptor intermolecular energy. This multi-objective strategy provides the molecular biologists with a range of solutions computing different RMSD scores and intermolecular energies. A set of representative multi-objective algorithms, namely NSGA-II, SMPSO, GDE3 and MOEA/D, have been evaluated in the scope of an extensive set of docking problems, which are featured by including HIV-proteases with flexible ARG8 side chains and their inhibitors. As use cases for biological validation, we have included a set of instances based on new retroviral inhibitors to HIV-proteases. The proposed multi-objective approach shows that the predictions of ligand's pose can be promising in cases in which studiesin silicoare necessary to test new candidate drugs (or analogue drugs) to a given therapeutic target.
PB Springer
SN 1432-7643
YR 2020
FD 2020-07-01
LK http://hdl.handle.net/10668/18635
UL http://hdl.handle.net/10668/18635
LA en
DS RISalud
RD Apr 7, 2025