Investigating the folding mechanism of the N‐terminal domain of ribosomal protein L9

Abstract

Protein folding is a popular topic in the life science. However, due to the limited sampling ability of experiments and simulations, the general folding mechanism is not yet clear to us. In this work, we study the folding of the N‐terminal domain of ribosomal protein L9 (NTL9) in detail by a mixing replica exchange molecular dynamics method. The simulation results are close to previous experimental observations. According to the Markov state model, the folding of the protein follows a nucleation‐condensation path. Moreover, after the comparison to its 39‐residue β‐α‐β motif, we find that the helix at the C‐terminal has a great influence on the folding process of the intact protein, including the nucleation of the key residues in the transition state ensemble and the packing of the hydrophobic residues in the native state.

A Study of a Protein-Folding Machine: Transient Rotation of the Polypeptide Backbone Facilitates Rapid Folding of Protein Domains in All-Atom Molecular Dynamics Simulations

“…The non-native conformations are sometimes observed in the MD simulations of protein domain folding, including the four targets discussed in this work [ 41 , 43 , 49 , 50 ]. We believe that such alternative conformations are in fact quite common, but when the “correct” conformation is known in advance, the “wrong” conformations may be seen as technical artifacts, or perhaps as occasional kinetic traps in the rugged folding landscapes [ 50 ].…”

“…The non-native conformations are sometimes observed in the MD simulations of protein domain folding, including the four targets discussed in this work [ 41 , 43 , 49 , 50 ]. We believe that such alternative conformations are in fact quite common, but when the “correct” conformation is known in advance, the “wrong” conformations may be seen as technical artifacts, or perhaps as occasional kinetic traps in the rugged folding landscapes [ 50 ]. On the contrary, we believe that the metastable alternative conformations of protein domains deserve special attention, because they may provide clues to the mechanisms of protein folding and misfolding in vitro and in vivo.…”