4.4 Article

The importance of protonation and tautomerization in relative binding affinity prediction: a comparison of AMBER TI and Schrodinger FEP

Journal

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
Volume 30, Issue 7, Pages 533-539

Publisher

SPRINGER
DOI: 10.1007/s10822-016-9920-5

Keywords

Protonation; Tautomerization; Free energy calculation; Thermodynamic integration; Free energy perturbation; Protein-ligand binding affinity

Funding

  1. Merck Research Laboratories (MRL) Postdoctoral Research Fellows Program
  2. Office of Advanced Cyberinfrastructure (OAC)
  3. Direct For Computer & Info Scie & Enginr [1515572] Funding Source: National Science Foundation

Ask authors/readers for more resources

In drug discovery, protonation states and tautomerization are easily overlooked. Through a Merck-Rutgers collaboration, this paper re-examined the initial settings and preparations for the Thermodynamic Integration (TI) calculation in AMBER Free-Energy Workflows, demonstrating the value of careful consideration of ligand protonation and tautomer state. Finally, promising results comparing AMBER TI and Schrodinger FEP+ are shown that should encourage others to explore the value of TI in routine Structure-based Drug Design.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available