Synergistic Use of Virtual Screening and Biophysical Methods for the Protein-Based Design of Peptidomimetics

Abstract

Combining virtual screening with biophysical studies of protein-ligand complexes is an effective tool for designing new peptidomimetics. When a three-dimensional structure of the target protein is known, automated docking of chemical databases can be used as a powerful filter to reduce the number of molecules that will be further tested. Easy screening of potential hits can then be performed using fluorescence polarization techniques, if a fluorescent-labeled ligand already exists for the target. In addition, thermodynamic properties of protein-ligand complexes can be measured by circular dichroism spectroscopy.

Keywords

• Circular dichroism
• Fluorescence polarization
• Peptidomimetic
• Pharmaceutical chemistry
• Virtual screening