The free energy of binding of a ligand to its target is an important optimization parameter in drug design, thus, its accurate prediction is highly desirable. Due to methodological advances and increased computer power, thermodynamic integration (TI) calculations can now be used to obtain relative free energies of binding of ligands in a timescale comparable to synthesis.To make these studies, especially for larger set of ligands, possible, we automated the setup procedure: starting from user defined binding modes, the procedure decides which ligands to connect via a perturbation based on maximum common substructure criteria and produces all necessary parameter and input files for free energy calculations in AMBER.We will present a number of examples to assess the performance of free energy calculations in drug design. We analyze the effect of different setup procedures and different force fields on the accuracy of the predictions.(*) current address: Bayer Pharma AG, Medicinal Chemistry, 13353 Berlin, Germany

Accuracy assessment of free energy calculations in drug design

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.