For the final selection from 1.8 M to 600 K, where information about coding SNPs was available, all C SNPs in coding regions that were not already in the backbone were added to the backbone.
Recently, backbone flexibility was added to the docking algorithm which led to improved predictions, including lower rmsds among top scoring ligands (63).
Interestingly, all randomized trials with one of the somewhat less intensive chemotherapy backbones (i.e. IFL bolus regimen, 5FU/LV bolus regimens; capecitabine) showed consistently an impressive improvement of PFS (HR 0,54; 0,50 and 0,63 respectively) when bevacizumab was added to that backbone [ 10, 12, 19].
Subgroups were made and named after the third compound that was added to the identical backbone in both arms.
Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B-MuD) for the treatment of MM relapsed patients.
On the other hand, no difference in PFS was observed when cixutumumab was added to gemcitabine and erlotinib as the backbone regimen in pancreatic cancer [56].
The miR159b backbone was synthesized by gene synthesis (MWG) and an additional MluI site was added to the 3′ end of the miR precursor.
During the local refinement procedure, a small initial perturbation was added to the subunits in low-resolution models first, then side chains were added, by a Monte Carlo Minimization which optimized both the backbones and side chains, and finally, a fast simulated annealing step was employed to relax the full atomic models with flexible backbones.
An enhanced force constant for backbone-connections (bb-cons) is added to reflect the chemical reality (also used in Hinsen's ENM and BENM, see below) hence the name Chemical Network Model (Kondrashov et al. 2006).
Additional "backbone" interrogating clones along each chromosome were added to aid in the detection of chromosome imbalance outside of targeted regions.
