The structure and assembly process of gas vesicles have received significant 
attention in recent decades, although relatively little is still known. This 
work combines state-of-the-art computational methods to develop a model for the 
major gas vesicle protein, GvpA, and explore its structure within the assembled 
vesicle. Elucidating this protein's structure has been challenging due to its 
adherent and aggregative nature, which has so far precluded in-depth biochemical 
analyses. Moreover, GvpA has extremely low similarity with any known protein 
structure, which renders homology modeling methods ineffective. Thus, alternate 
approaches were used to model its tertiary structure. Starting with the sequence 
from haloarchaeon Halobacterium sp. NRC-1, we performed ab initio modeling and 
threading to acquire a multitude of structure decoys, which were equilibrated 
and ranked using molecular dynamics and mechanics, respectively. The highest 
ranked predictions exhibited an α-β-β-α secondary structure in agreement with 
earlier experimental findings, as well as with our own secondary structure 
predictions. Afterwards, GvpA subunits were docked in a quasi-periodic 
arrangement to investigate the assembly of the vesicle wall and to conduct 
simulations of contact-mode atomic force microscopy imaging, which allowed us to 
reconcile the structure predictions with the available experimental data. 
Finally, the GvpA structure for two representative organisms, Anabaena 
flos-aquae and Calothrix sp. PCC 7601, was also predicted, which reproduced the 
major features of our GvpA model, supporting the expectation that homologous 
GvpA sequences synthesized by different organisms should exhibit similar 
structures.