Structural Basis of Antibody Conformation and Stability Modulation by Framework Somatic Hypermutation.

ABSTRACT: Accumulation of somatic hypermutation (SHM) is the primary mechanism to enhance the binding affinity of antibodies to antigens in vivo. However, the structural basis of the effects of many SHMs remains elusive. Here, we integrated atomistic molecular dynamics (MD) simulation and data mining to build a high-throughput structural bioinformatics pipeline to study the effects of individual and combination SHMs on antibody conformation, flexibility, stability, and affinity. By applying this pipeline, we characterized a common mechanism of modulation of heavy-light pairing orientation by frequent SHMs at framework positions 39_H, 91_H, 38_L, and 87_L through disruption of a conserved hydrogen-bond network. Q39L_H alone and in combination w

SUBMITTER: Sheng Z 

PROVIDER: S-EPMC8761896 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature