Title:Exploring the Relationship between Sequences, Structures, Dynamical Behaviors and Functions of New Type Protein Drugs: DARPins
VOLUME: 19 ISSUE: 12
Author(s):Xue Wu, Yue Shi, Pengyu Ren, Deping Wang and Guohui Li
Affiliation:Dalian Institute of Chemical Physics, Chinese Academy of Sciences 457 Zhongshan Rd.
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
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.
