Nanopore-Based Sensors for Ligand-Receptor Lead Optimization.
Developing a low-cost and high-efficacy method to optimize prescreened or designed drug candidates will facilitate drug discovery and biomedical research in general. Current methods of drug screening usually involve tedious sample preparation and costly biological/chemical assays. Here, through all-atom molecular dynamics simulations, we propose a new drug optimization method, based on the nanopore force spectroscopy, to electrically detect the binding strength between a drug molecule and a target protein. Simulation results demonstrate that the drug-protein complex can be electrophoretically driven into a nanopore, which is followed by the rupture of the complex at a critical biasing voltage. The latter determines the binding strength of the tested drug molecule. It is expected that the application of this single-molecule technology could help to accelerate the drug discovery, particularly for processes of the narrow screening and further lead optimization.
Computational Biology Center, IBM Thomas J. Watson Research, Yorktown Heights, New York 10598, United States.
Binquan
B
Luan
Computational Biology Center, IBM Thomas J. Watson Research, Yorktown Heights, New York 10598, United States.
Tien
T
Huynh
Computational Biology Center, IBM Thomas J. Watson Research, Yorktown Heights, New York 10598, United States.
Ruhong
R
Zhou
D055808:Drug Discovery / Q000379:methods*; D008024:Ligands; D056004:Molecular Dynamics Simulation; D058608:Nanopores; D036103:Nanotechnology / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins
biosensor; drug discovery; ligand binding affinity; nanopore force spectroscopy