Enhancements to the Rosetta Energy Function Enable Improved Identification of Small Molecules that Inhibit Protein-Protein Interactions.

ABSTRACT: Protein-protein interactions are among today's most exciting and promising targets for therapeutic intervention. To date, identifying small-molecules that selectively disrupt these interactions has proven particularly challenging for virtual screening tools, since these have typically been optimized to perform well on more "traditional" drug discovery targets. Here, we test the performance of the Rosetta energy function for identifying compounds that inhibit protein interactions, when these active compounds have been hidden amongst pools of "decoys." Through this virtual screening benchmark, we gauge the effect of two recent enhancements to the functional form of the Rosetta energy function: the new "Talaris" update and the "pwSHO" solvation model. Finally, we conclude by developing and va

SUBMITTER: Bazzoli A 

PROVIDER: S-EPMC4617380 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature