Journal
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Volume 60, Issue 11, Pages 5395-5406Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jcim.0c00456
Keywords
-
Categories
Funding
- DOC Fellowship of the Austrian Academy of Sciences (OAW) at the Institute for Molecular Modeling and Simulation at the University of Natural Resources and Life Sciences, Vienna [24987]
Ask authors/readers for more resources
Free-energy perturbation (FEP) methods are commonly used in drug design to calculate relative binding free energies of different ligands to a common host protein. Alchemical ligand transformations are usually performed in multiple steps which need to be chosen carefully to ensure sufficient phase-space overlap between neighboring states. With one-step or single-step FEP techniques, a single reference state is designed that samples phase-space not only representative of a full transformation but also ideally resembles multiple ligand end states and hence allows for efficient multistate perturbations. Enveloping distribution sampling (EDS) is one example for such a method in which the reference state is created by a mathematical combination of the different ligand end states based on solid statistical mechanics. We have recently proposed a novel approach to EDS which enables efficient barrier crossing between the different end states, termed accelerated EDS (A-EDS). In this work, we further simplify the parametrization of the A-EDS reference state and demonstrate the automated calculation of multiple free-energy differences between different ligands from a single simulation in three different well-described drug design model systems.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available