Using homology modeling to interrogate binding affinity in neutralization of ricin toxin by a family of single domain antibodies.

ABSTRACT: In this report we investigated, within a group of closely related single domain camelid antibodies (V_H Hs), the relationship between binding affinity and neutralizing activity as it pertains to ricin, a fast-acting toxin and biothreat agent. The V1C7-like V_H Hs (V1C7, V2B9, V2E8, and V5C1) are similar in amino acid sequence, but differ in their binding affinities and toxin-neutralizing activities. Using the X-ray crystal structure of V1C7 in complex with ricin's enzymatic subunit (RTA) as a template, Rosetta-based homology modeling coupled with energetic decomposition led us to predict that a single pairwise interaction between Arg29 on V5C1 and Glu67 on RTA was responsible for the difference in ricin toxin binding affinity between V1C7, a weak neutralizer, and V5C1,

SUBMITTER: Bazzoli A 

PROVIDER: S-EPMC5754017 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature