Molecular Dynamics Simulation Of Co-translational Folding Of Four Proteins

Protein plays an important role in the life activities of cells and organisms.Only by folding the protein from the primary structure into the correct tertiary structure can it achieve various functions in the cell.Misfolding will cause a series of diseases.Protein folding can be divided into intracellular folding(folding in vivo)and extracellular free folding(folding in vitro).The folding of nascent peptide chain in vivo is called co-translational folding.Compared with in vitro folding,the nascent chain in the cotranslational folding will interact with the ribosome tunnel,ribosome surface and molecular chaperones.Studies have shown that co-translational folding can greatly reduce protein misfolding and improve folding efficiency.However,there are only a few studies of cotranslational folding that compare experiment with theory.In this article,molecular dynamics simulation methods will be used to study the problem of protein co-translational folding.The research objects are four proteins,transmembrane proteins VSV-G and gp41 and soluble proteins NAGK and rib L9.The co-translational folding of these four protein molecules in the real ribosome tunnel has been studied experimentally.This article hopes to compare the results of molecular dynamics simulation with the experimental results and further understand the experimental results.The research content is as follows:(1)Molecular dynamics simulation of the free folding of four protein molecules and the result will be used as reference for co-translational folding.Free folding simulation results show that the N fragments and C fragments of the four proteins fold at the same time and quickly,and they all can form helices and ? conformations;The protein VSV-G forms more helices than the other three proteins,especially in the transmembrane sequence,and the folding degree of its N segment is less than its C segment while the protein gp41 is inverse.For the protein NAGK and protein rib L9,their N and C fragments have similar folding degrees.(2)Molecular dynamics simulation of co-translational folding of four protein molecules in the ribosome tunnel model.The simulations are done for the translation speeds of one residue every 2ns,5ns,10 ns and 20 ns respectively.The simulation results show that the four proteins can form helix and a little ? conformations in the ribosome tunnel;The amount of helix structure is more than that of free folding,while that ? conformation is inverse.The ribosome tunnel can promote the formation of secondary structure of the protein and the slower translation speed and higher probability of forming helix structure.It is different from previous strudies that all the four proteins can form helix structure in the tunnel.In particular,VSV-G can form stable helix structure in the native position.It is also found that the folding degrees of N fragment of the protein VSV-G and gp41 are less than C fragment,but the N-segment folding degrees of the soluble proteins NAGK and rib L9 are greater than their C-segments.(3)The four protein molecules are folded in the real ribosome tunnel.The simulation results show that under the current simulation time only the transmembrane protein VSV-G has formed short helix structure in the real ribosome tunnel,and the other three proteins have not formed any secondary structure,but the RMSD and the solvent accessible surface area values of the four proteins show that they have the tendency to fold.In summary,our results are generally in agreement with previous experiment and simulation,but show some that are different from previous suggestions.