Selection of peptides targeting helix 31 of bacterial 16S ribosomal RNA by screening M13 phage-display libraries

Ribosomal RNA is the catalytic portion of ribosomes, and undergoes a variety of conformational changes during translation. Structural changes in ribosomal RNA can be facilitated by the presence of modified nucleotides. Helix 31 of bacterial 16S ribosomal RNA harbors two modified nucleotides, m2G966 and m?C967, that are highly conserved among bacteria, though the degree and nature of the modifications in this region are different in eukaryotes. Contacts between helix 31 and the P-site tRNA, initiation factors, and ribosomal proteins highlight the importance of this region in translation. In this work, a heptapeptide M13 phage-display library was screened for ligands that target the wild-type, naturally modified bacterial helix 31. Several peptides, including TYLPWPA, CVRPFAL, TLWDLIP, FVRPFPL, ATPLWLK, and DIRTQRE, were found to be prevalent after several rounds of screening. Several of the peptides exhibited moderate affinity (in the high nM to low μM range) to modified helix 31 in biophysical assays, including surface plasmon resonance (SPR), and were also shown to bind 30S ribosomal subunits. These peptides also inhibited protein synthesis in cell-free translation assays.     

Convergence in the incompressible limit of finite element approximations based on the Hu-Washizu formulation

The classical Hu–Washizu mixed formulation for plane problems in elasticity is examined afresh, with the emphasis on behavior in the incompressible limit. The classical continuous problem is embedded in a family of Hu–Washizu problems parametrized by a scalar α for which corresponds to the classical formulation, with λ and μ being the Lamé parameters. Uniform well- posedness in the incompressible limit of the continuous problem is established for α ≠ − 1. Finite element approximations are based on the choice of piecewise bilinear approximations for the displacements on quadrilateral meshes. Conditions for uniform convergence are made explicit. These conditions are shown to be met by particular choices of bases for stresses and strains, and include bases that are well known, as well as newly constructed bases. Though a discrete version of the spherical part of the stress exhibits checkerboard modes, it is shown that a λ-independent a priori error estimate for the displacement can be established. Furthermore, a λ-independent estimate is established for the post-processed stress. The theoretical results are explored further through selected numerical examples.