Antibodies exhibit multiple paratope states influencing V_H-V_L domain orientations.

ABSTRACT: In the last decades, antibodies have emerged as one of the most important and successful classes of biopharmaceuticals. The highest variability and diversity of an antibody is concentrated on six hypervariable loops, also known as complementarity determining regions (CDRs) shaping the antigen-binding site, the paratope. Whereas it was assumed that certain sequences can only adopt a limited set of backbone conformations, in this study we present a kinetic classification of several paratope states in solution. Using molecular dynamics simulations in combination with experimental structural information we capture the involved conformational transitions between different canonical clusters and additional dominant solution structures occurring in the micro-to-millisecond timescale. Furthermore,

SUBMITTER: Fernandez-Quintero ML 

PROVIDER: S-EPMC7576833 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature