activity reveals an importance to the general scaffold presented in the two structures. In other words, NERI01 can be used as a starting point for inhibitors of the ERCC1-XPA interaction. All docking simulations employed the software AutoDock, version 4.0. The docking method and parameters were similar to the ones used in our previous work. The screening method adopted two filtering phases with the same docking parameters. First, we screened the entire CN library against a single target model followed by applying the relaxed complex scheme through docking of the top 2,000 hits from the first screen against the rest of the ten target structures. Using the SHP099 Lamarckian Genetic Algorithm, the docking parameters included an initial population of 150 random individuals; a maximum number of 10,000,000 energy evaluations; 100 trials; 27,000 maximum generations; a mutation rate of 0.02; a crossover rate of 0.80 and the requirement that only one individual can survive into the next generation. Clustering of the docking results followed the same adaptive procedure as the one employed in our previous study. In brief, for each docking simulation a modified version of the PTRAJ module of AMBER clustered the docking trials. Every time a number of clusters were produced, two clustering metrics were calculated to assess the quality of clustering. Once acceptable values for these metrics were reached, the clustering protocol extracted the clusters at the predicted cluster counts. The screening protocol then sorted the docking results by the Astragalus Polysacharin structure lowest binding energy of the most populated cluster. If more than one target was involved, as it was the case for the second phase of docking, a different ranking scheme was followed. The objective was to extract the docking solution, for each ligand, that had the largest cluster population and the lowest binding energy from all targets. In this context, for each ligand, the docking results were clustered independently for the individual targets. The clustering results were then compared and only the ones that corresponded to at least 25 as a cluster population were considered. AutoDock scoring function provided a preliminary ranking for the compounds. The lowest energy pose for each ligand with its representative ERCC1 structure was used a
