Improving the Efficiency of Ligand-Binding Protein Design with Molecular Dynamics Simulations.

ABSTRACT: Custom-designed ligand-binding proteins represent a promising class of macromolecules with exciting applications toward the design of new enzymes or the engineering of antibodies and small-molecule recruited proteins for therapeutic interventions. However, several challenges remain in designing a protein sequence such that the binding site organization results in high affinity interaction with a bound ligand. Here, we study the dynamics of explicitly solvated designed proteins through all-atom molecular dynamics (MD) simulations to gain insight into the causes that lead to the low affinity or instability of most of these designs, despite the prediction of their success by the computational design methodology. Simulations ranging from 500 to 1000 ns per replicate were conducted on 37 design

SUBMITTER: Barros EP 

PROVIDER: S-EPMC7532806 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature