Generalized Structural Polymorphism in Virus Capsid Self-Assembly

Self-assembly of viral capsids, which are spherical proteins shells with icosahedral symmetry, holds significant potential for applications in materials science and medicine. However, the complexity of preparing these systems for assembly and the difficulty of quantitative experimental measurements on the assembly process have limited access to critical mechanistic questions that dictate the final product yields and isomorphic forms. Molecular dynamics simulations provide a means of elucidating self-assembly of viral proteins into icosahedral capsids and were the focus of our studies (1-3) by employing our multiscale models for the coat proteins. We examined the spontaneous self-assembly of viral capsids of different sizes containing T = 1, 3, 4, 7, 9, 12, 13, 16, and 19 proteins in each of their 60 icosahedral repeating units (number of proteins per icosahedral capsid = 60xT).

We observed, in addition to icosahedral capsids, a variety of nonicosahedral yet highly ordered and enclosed capsules. Such structural polymorphism was demonstrated to be an inherent property of the coat proteins, independent of the capsid complexity and the elementary kinetic mechanisms. Moreover, there exist two distinctive classes of polymorphic structures: aberrant capsules that are larger than their respective icosahedral capsids when T = 1-7; and capsules that are smaller than their respective icosahedral capsids when T = 7-19. Different kinetic mechanisms responsible for self-assembly of those classes of aberrant structures were deciphered, providing insights into the control of the self-assembly of icosahedral capsids.

References:

1. H.D. Nguyen, V.S. Reddy and C.L. Brooks III, “Deciphering the kinetic mechanism of spontaneous self-assembly of icosahedral capsids,” Nano Letters, 7(2) 338-44 (2007)

2. H.D. Nguyen, V.S. Reddy and C.L. Brooks III, “Invariant polymorphism in virus capsid assembly,” J. Am. Chem. Soc., 131(7): 2606-14 (2009)

3. H.D. Nguyen and C.L. Brooks III, “Generalized structural polymorphism of self-assembled viral capsids,” Nano Letters, 8(12), 4574-81 (2008)