Small angle X-ray scattering and molecular dynamic simulations provide molecular insight for stability of recombinant human transferrin.

ABSTRACT: Transferrin is an attractive candidate for drug delivery due to its ability to cross the blood brain barrier. However, in order to be able to use it for therapeutic purposes, it is important to investigate how its stability depends on different formulation conditions. Combining high-throughput thermal and chemical denaturation studies with small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, it was possible to connect the stability of transferrin with its conformational changes. Lowering pH induces opening of the transferrin N-lobe, which results in a negative effect on the stability. Presence of NaCl or arginine at low pH enhances the opening and has a negative impact on the overall protein stability.

Statement of significance

Protein-based therapeutics have

SUBMITTER: Kulakova A 

PROVIDER: S-EPMC7337065 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature