Fig. 3.

Hsp90 influences the capsid sequence space. a Role of Hsp90 in pathways of protein folding and aggregation. b Analysis pipeline to identify codon sites that differ significantly in their ability to support destabilizing variants (Site_destab) or aggregation-prone (Site_agg) variants between Hsp90_N and hsp90_i populations. Significant sites were identified as described in Methods. c, d Number of Site_destab (c) and Site_agg (d) observed in viral proteins: P1 capsid protein; 3C protease; and 3D polymerase. e Distribution of Site_destab and Site_agg at buried (Brd), interface (Int), or surface (Sfc) positions across folded P1 (based on crystal structure 2PLV). Significance: ***p < 0.005 by two-tail Fisher’s exact test