Common framework mutations impact antibody interfacial dynamics and flexibility.

ABSTRACT:

Introduction

With the flood of engineered antibodies, there is a heightened need to elucidate the structural features of antibodies that contribute to specificity, stability, and breadth. While antibody flexibility and interface angle have begun to be explored, design rules have yet to emerge, as their impact on the metrics above remains unclear. Furthermore, the purpose of framework mutations in mature antibodies is highly convoluted.

Methods

To this end, a case study utilizing molecular dynamics simulations was undertaken to determine the impact framework mutations have on the VH-VL interface. We further sought to elucidate the governing mechanisms by which changes in the VH-VL interface angle impact structural elements of mature antibodies by looking at root mean squared

SUBMITTER: Rhodes ER 

PROVIDER: S-EPMC9996335 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature