TY - JOUR
T1 - A Multiscale Model for the Self-Assembly of Coat Proteins in Bacteriophage MS2
AU - Wang, Bo
AU - Zhang, Junjie
AU - Wu, Yinghao
N1 - Funding Information:
This work was supported by the National Institutes of Health under grant numbers R01GM120238 and R01GM122804. The work is also partially supported by a start-up grant from Albert Einstein College of Medicine. Computational support was provided by Albert Einstein College of Medicine High Performance Computing Center. J.Z. is supported by start-up funding from the Department of Biochemistry and Biophysics at Texas A&M University and the Center for Phage Technology, jointly sponsored by Texas AgriLife and Texas A&M University. J.Z. acknowledge the NIH grants R21AI137696 and P01AI095208, the Welch Foundation grants A-1863, the Texas A&M Triads for Transformation grant, the TAMU School of Science Strategic Transformative Research Program, and the CST*R Foundation.
Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/9/23
Y1 - 2019/9/23
N2 - The self-assembly of viral capsids is an essential step to the formation of infectious viruses. Elucidating the kinetic mechanisms of how a capsid or virus-like particle assembles could advance our knowledge about the viral lifecycle, as well as the general principles in self-assembly of biomaterials. However, current understanding of capsid assembly remains incomplete for many viruses due to the fact that the transient intermediates along the assembling pathways are experimentally difficult to be detected. In this paper, we constructed a new multiscale computational framework to simulate the self-assembly of virus-like particles. We applied our method to the coat proteins of bacteriophage MS2 as a specific model system. This virus-like particle of bacteriophage MS2 has a unique feature that its 90 sequence-identical dimers can be classified into two structurally various groups: one is the symmetric CC dimer, and the other is the asymmetric AB dimer. The homotypic interactions between AB dimers result in a 5-fold symmetric contact, while the heterotypic interactions between AB and CC dimers result in 6-fold symmetric contact. We found that the assembly can be described as a physical process of phase transition that is regulated by various factors such as concentration and specific stoichiometry between AB and CC dimers. Our simulations also demonstrate that heterotypic and homotypic interfaces play distinctive roles in modulating the assembling kinetics. The interaction between AB and CC dimers is much more dynamic than that between two AB dimers. We therefore suggest that the alternate growth of viral capsid through the heterotypic dimer interactions dominates the assembling pathways. This is, to the best of our knowledge, the first multiscale model to simulate the assembling process of coat proteins in bacteriophage MS2. The generality of this approach opens the door to its further applications in assembly of other viral capsids, virus-like particles, and novel drug delivery systems.
AB - The self-assembly of viral capsids is an essential step to the formation of infectious viruses. Elucidating the kinetic mechanisms of how a capsid or virus-like particle assembles could advance our knowledge about the viral lifecycle, as well as the general principles in self-assembly of biomaterials. However, current understanding of capsid assembly remains incomplete for many viruses due to the fact that the transient intermediates along the assembling pathways are experimentally difficult to be detected. In this paper, we constructed a new multiscale computational framework to simulate the self-assembly of virus-like particles. We applied our method to the coat proteins of bacteriophage MS2 as a specific model system. This virus-like particle of bacteriophage MS2 has a unique feature that its 90 sequence-identical dimers can be classified into two structurally various groups: one is the symmetric CC dimer, and the other is the asymmetric AB dimer. The homotypic interactions between AB dimers result in a 5-fold symmetric contact, while the heterotypic interactions between AB and CC dimers result in 6-fold symmetric contact. We found that the assembly can be described as a physical process of phase transition that is regulated by various factors such as concentration and specific stoichiometry between AB and CC dimers. Our simulations also demonstrate that heterotypic and homotypic interfaces play distinctive roles in modulating the assembling kinetics. The interaction between AB and CC dimers is much more dynamic than that between two AB dimers. We therefore suggest that the alternate growth of viral capsid through the heterotypic dimer interactions dominates the assembling pathways. This is, to the best of our knowledge, the first multiscale model to simulate the assembling process of coat proteins in bacteriophage MS2. The generality of this approach opens the door to its further applications in assembly of other viral capsids, virus-like particles, and novel drug delivery systems.
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U2 - 10.1021/acs.jcim.9b00514
DO - 10.1021/acs.jcim.9b00514
M3 - Article
C2 - 31411466
AN - SCOPUS:85072349483
SN - 1549-9596
VL - 59
SP - 3899
EP - 3909
JO - Journal of Chemical Information and Modeling
JF - Journal of Chemical Information and Modeling
IS - 9
ER -