Journal
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
Volume 32, Issue 1, Pages 265-272Publisher
SPRINGER
DOI: 10.1007/s10822-017-0064-z
Keywords
D3R; Drug design data resource; Free energy calculations; Computer-aided drug design; Binding affinity prediction
Ask authors/readers for more resources
Physics-based free energy simulations have increasingly become an important tool for predicting binding affinity and the recent introduction of automated protocols has also paved the way towards a more widespread use in the pharmaceutical industry. The D3R 2016 Grand Challenge 2 provided an opportunity to blindly test the commercial free energy calculation protocol FEP+ and assess its performance relative to other affinity prediction methods. The present D3R free energy prediction challenge was built around two experimental data sets involving inhibitors of farnesoid X receptor (FXR) which is a promising anticancer drug target. The FXR binding site is predominantly hydrophobic with few conserved interaction motifs and strong induced fit effects making it a challenging target for molecular modeling and drug design. For both data sets, we achieved reasonable prediction accuracy (RMSD approximate to 1.4 kcal/mol, rank 3-4 according to RMSD out of 20 submissions) comparable to that of state-of-the-art methods in the field. Our D3R results boosted our confidence in the method and strengthen our desire to expand its applications in future in-house drug design projects.
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