Exploring the Relationship between Sequences, Structures, Dynamical Behaviors and Functions of New Type Protein Drugs: DARPins

Xue      Wu; Yue      Shi; Pengyu      Ren; Deping      Wang; Guohui      Li

Abstract

DARPins (designed ankyrin repeat proteins), new kinds of binding proteins, have the potential to overcome the defects of monoclonal antibodies, and hence may become the alternatives to antibodies and generate a novel therapeutic approach. DARPins can be selected to bind any given target proteins with high affinity and specificity. In the process of binding to target proteins, the reason why DARPins have high affinity to target proteins as well as the correlation among sequences, structures, dynamical behaviors and binding to target proteins are still unknown. This paper studied DARPins using the AMBER package with ff03 force field for molecular dynamics simulations, providing a theoretical basis for the research on a new type of protein drug. This shows that the DARPins have more dynamical behaviors regularity after binding to target proteins compared with non-binding DARPins, but the binding to target proteins does not always stabilize the structures of DARPins, and the changes in the regions of β-turn and loop are the most obvious. The changes in hydrogen bonds and hydrophobic interactions have close relationship with the changes in the stability and cross correlation of DARPins.

Keywords: Molecular dynamics simulation DARPins protein drug, dynamical cross correlation stability, binding proteins, monoclonal antibodies, alternatives, AMBER package, theoretical basis, target proteins, β-turn, loop