Computational evidence that fast translation speed can increase the probability of cotranslational protein folding.
Translation speed can affect the cotranslational folding of nascent peptide. Experimental observations have indicated that slowing down translation rates of codons can increase the probability of protein cotranslational folding. Recently, a kinetic modeling indicates that fast translation can also increase the probability of cotranslational protein folding by avoiding misfolded intermediates. We show that the villin headpiece subdomain HP35 is an ideal model to demonstrate this phenomenon. We studied cotranslational folding of HP35 with different fast translation speeds by all-atom molecular dynamics simulations and found that HP35 can fold along a well-defined pathway that passes the on-pathway intermediate but avoids the misfolded off-pathway intermediate in certain case. This greatly increases the probability of HP35 cotranslational folding and the approximate mean first passage time of folding into native state is about 1.67μs. Since we also considered the space-confined effect of the ribosomal exit tunnel on the cotranslational folding, our simulation results suggested alternative mechanism for the increasing of cotranslational folding probability by fast translation speed.
Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.
Ercheng
E
Wang
Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.
Jun
J
Wang
Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.
Changjun
C
Chen
Biomolecular Physics and Modeling Group, Department of Physics, Huazhong University of Science and Technology, Wuhan 430074, China.
Yi
Y
Xiao
D003062:Codon / Q000235:genetics; D019295:Computational Biology; D008958:Models, Molecular; D016900:Neurofilament Proteins / Q000737:chemistry* / Q000235:genetics; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics*; D013816:Thermodynamics
D003062:Codon; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C115223:villin headpiece subdomain peptide