CDR-H3 loop ensemble in solution - conformational selection upon antibody binding.

ABSTRACT: We analyzed pairs of protein-binding, peptide-binding and hapten-binding antibodies crystallized as complex and in the absence of the antigen with and without conformational differences upon binding in the complementarity-determining region (CDR)-H3 loop. Here, we introduce a molecular dynamics-based approach to capture a diverse conformational ensemble of the CDR-H3 loop in solution. The results clearly indicate that the inherently flexible CDR-H3 loop indeed needs to be characterized as a conformational ensemble. The conformational changes of the CDR-H3 loop in all antibodies investigated follow the paradigm of conformation selection, because we observe the experimentally determined binding competent conformation without the presence of the antigen within the ensemble of pre-existing con

SUBMITTER: Fernandez-Quintero ML 

PROVIDER: S-EPMC6748594 | biostudies-literature | 2019 Aug/Sep

REPOSITORIES: biostudies-literature