Structural mechanism of Fab domain dissociation as a measure of interface stability.

ABSTRACT: Therapeutic antibodies should not only recognize antigens specifically, but also need to be free from developability issues, such as poor stability. Thus, the mechanistic understanding and characterization of stability are critical determinants for rational antibody design. In this study, we use molecular dynamics simulations to investigate the melting process of 16 antigen binding fragments (Fabs). We describe the Fab dissociation mechanisms, showing a separation in the V_H-V_L and in the C_H1-C_L domains. We found that the depths of the minima in the free energy curve, corresponding to the bound states, correlate with the experimentally determined melting temperatures. Additionally, we provide a detailed structural description of the dissociation m

SUBMITTER: Pomarici ND 

PROVIDER: S-EPMC10049950 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature