Grand Challenge 2 from D3R provided a farnesoid X receptor (FXR) target dataset to participants, which was used to test the performance of various computational approaches. SilcsBio’s SILCS-MC approach ranked 4th in Stage 1 and 6th in Stage 2 on the Free Energy Set 1 of this challenge.
We used our unique SILCS approach to map preferred interaction partners to the FXR protein surface, taking into account the protein’s flexibility and desolvation effects, to yield 3-D probability-based FragMaps. SILCS-MC then sampled the ligands of this set in the binding pocket to predict binding poses and rank-order affinities. Among 30 submissions using explicit solvent free energy methods, what makes the SILCS approach stand out?
Dr. Lakkaraju, Director of Product Development at SilcsBio, says the SILCS-MC predictions stand out for two reasons. He says, “The method did not need training against published binding data, and after FragMaps generation, rank-ordering of ligand data-set with SILCS-MC is at least several orders of magnitude faster than the other free-energy methods featured in the top 10 entries.” Importantly, the SILCS approach is a ligand-independent approach, and SILCS FragMaps can be used to evaluate a wide range of ligands.
The SILCS approach can also contribute meaningfully to drug design efforts beyond the scope of this challenge. It has qualitative and quantitative uses towards virtual screening, ligand optimization, fragment-based design in the context of the SILCS grid free energy FragMaps.
About SilcsBio, LLC: SilcsBio started operations in April 2013 based on licensed intellectual property developed by Dr. Alexander D. MacKerell, Jr at the University of Maryland, Baltimore where he is the Grollman-Glick Professor of Pharmaceutical Sciences and Director of the Computer-Aided Drug Design Center. SilcsBio develops software for computer aided drug design and has customers in the US, Europe, and Japan; the software is available for licensing or can be harnessed via contracted services performed by SilcsBio scientists. The company is headquartered at Spark-Baltimore located at 8 Market Place, Suite 300, Baltimore, MD 21202.
For more information, please contact: Tina Guvench, firstname.lastname@example.org, 410.645.0387
Details about the Drug Design Data Resource (D3R) and Grand Challenge 2 can be found at: https://drugdesigndata.org