Author:
Shahraki Aida,Selent Jana,Kolb Peter
Abstract
AbstractComputer-aided approaches to ligand design need to balance accuracy with speed. This is particularly true for one of the key parameters to be optimized during ligand development, the free energy of binding ($$\Delta$$
Δ
G$$_{\text {bind}}$$
bind
). Here, we developed simple models based on the Linear Interaction Energy approximation to free energy calculation for a G protein-coupled receptor, the serotonin receptor 2A, and critically evaluated their accuracy. Several lessons can be taken from our calculations, providing information on the influence of the docking software used, the conformational state of the receptor, the cocrystallized ligand, and its comparability to the training/test ligands.
Funder
Instituto de Salud Carlos III
European Commission
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Philipps-Universität Marburg
Publisher
Springer Science and Business Media LLC
Subject
Physical and Theoretical Chemistry,Computer Science Applications,Drug Discovery