Characterizing the function of domain linkers in regulating the dynamics of multi-domain fusion proteins by microsecond molecular dynamics simulations and artificial intelligence.

ABSTRACT: Multi-domain proteins are not only formed through natural evolution but can also be generated by recombinant DNA technology. Because many fusion proteins can enhance the selectivity of cell targeting, these artificially produced molecules, called multi-specific biologics, are promising drug candidates, especially for immunotherapy. Moreover, the rational design of domain linkers in fusion proteins is becoming an essential step toward a quantitative understanding of the dynamics in these biopharmaceutics. We developed a computational framework to characterize the impacts of peptide linkers on the dynamics of multi-specific biologics. Specifically, we first constructed a benchmark containing six types of linkers that represent various lengths and degrees of flexibility and used them to conne

SUBMITTER: Wang B 

PROVIDER: S-EPMC8500615 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature