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Although the branched capsular polysaccharides of <i>Streptococcus agalactiae</i> serotype III (GBSIII PS) and <i>Streptococcus pneumoniae</i> serotype 14 (Pn14 PS) differ only in the addition of a terminal sialic acid on the GBSIII PS side chains, these very similar polysaccharides are immunogenically distinct. Our simulations of GBSIII PS, Pn14 PS and the unbranched backbone polysaccharide provide a conformational rationale for the different antigenic epitopes identified for these PS. We find that side chains stabilize the proximal <inline-formula> <math display="inline"> <semantics> <mi>&#946;</mi> </semantics> </math> </inline-formula><span style="font-variant: small-caps;">d</span>Glc(1&#8594;6)<inline-formula> <math display="inline"> <semantics> <mi>&#946;</mi> </semantics> </math> </inline-formula><span style="font-variant: small-caps;">d</span>GlcNAc backbone linkage, restricting rotation and creating a well-defined conformational epitope at the branch point. This agrees with the glycotope structure recognized by an anti-GBSIII PS functional monoclonal antibody. We find the same dominant solution conformation for GBSIII and Pn14 PS: aside from the branch point, the backbone is very flexible with a &#8220;zig-zag&#8222; conformational habit, rather than the helix previously proposed for GBSIII PS. This suggests a common strategy for bacterial evasion of the host immune system: a flexible backbone that is less perceptible to the immune system, combined with conformationally-defined branch points presenting human-mimic epitopes. This work demonstrates how small structural features such as side chains can alter the conformation of a polysaccharide by restricting rotation around backbone linkages.