1. A Model for How Ribosomal Release Factors Induce Peptidyl-tRNA Cleavage in Termination of Protein Synthesis 
Stefan Trobro, Johan Åqvist 
Molecular Cell 
Volume 27, Issue 5, Pages (September 2007)
DOI: /j.molcel
Copyright © 2007 Elsevier Inc. Terms and Conditions

2. Figure 1
Stimulation of Peptidyl-tRNA Hydrolysis by Binding of Deacylated tRNA to the A Site
(A) Predicted mechanism for peptidyl-tRNA hydrolysis stimulated by a deacylated A site tRNA. A representative MD snapshot at the beginning of the reaction (yellow) is superimposed on a crystal structure with an A site substrate analog (cyan, 1VQN) (Schmeing et al., 2005b). The hydrolytic water molecule (wat) that attacks the P site ester bond is coordinated by hydrogen bonds to the A site A76 O3′ and P site A76 O2′, which acts as a proton shuttle to the leaving P site A76 O3′ oxygen. R, TI, and P denote reactants, tetrahedral intermediate, and products, respectively.
(B) Calculated free energy profiles for the uncatalyzed reaction in solution and for the ribosome reaction with and without a bound deacylated A site tRNA (estimated error bars for the FEP calculations are ± 1.3 kcal/mol).
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2007 Elsevier Inc. Terms and Conditions

3. Figure 2 Structural Effects of Deacylated tRNA Binding to the A Site
Stereo view comparing representative MD structures at the beginning of the reaction with CCA bound to A site (yellow carbons, red water oxygens) and with an empty A site (cyan carbons, green waters).
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2007 Elsevier Inc. Terms and Conditions

4. Figure 3
Docking of a Peptide Containing the Conserved Release Factor GGQ Motif into the A Site
(A) Illustration of the docking problem where part of the large ribosomal subunit is shown as an all-atom model (cyan), RF1 in yellow (Cα trace), and the P site tRNA in orange (backbone ribbon). The heptapeptide fragment (containing the GGQ motif) used in the docking calculations is shown in red, while the PVT motif involved in stop codon reading is shown in magenta. Coordinates are from the low-resolution T. thermophilus complex (Petry et al., 2005).
(B) View of different types of docking solutions obtained, where nine out of ten form a peptide backbone turn with insertion of the Glnmethyl residue into the A site. Structures from all three docking clusters were selected for further simulations.
(C) Representative MD snapshot of the early reaction stage (with key hydrogen bonds indicated), showing the conformation originating from cluster 1 that is found to be catalytically active in the ribosome.
Molecular Cell  , DOI: ( /j.molcel )
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5. Figure 4
Structural Mimicry and Energetics of the Release Factor-Catalyzed Reaction
(A) Structural mimicry between the RF side chain (yellow) and that of an aminoacylated tRNA bound to A site (cyan, 1VQN) (Schmeing et al., 2005b).
(B) Calculated free energy diagram for the peptidyl-tRNA hydrolysis reaction with the native GGQmethyl sequence and with the GAQmethyl and GGA variants. The uncatalyzed water reaction is also shown as a reference (estimated error bars for the FEP calculations are ±1.3 kcal/mol).
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2007 Elsevier Inc. Terms and Conditions

6. Figure 5 Predicted Structural Effects of Release Factor Mutations
(A) Predicted structure of the GAQmethyl mutant RF (cyan) compared to that of the wild-type (yellow), where stabilizing hydrogen bonding interactions of the GGQmethyl backbone with A2602 and G2583 are highlighted.
(B) Predicted structure of the GGA mutant RF in which an extra water molecule can fit between the Ala side chain and the hydrolytic water.
Molecular Cell  , DOI: ( /j.molcel )
Copyright © 2007 Elsevier Inc. Terms and Conditions