Frey Lab

Division of Pharmaceutical Sciences @ LIU Pharmacy

Welcome to the Frey Lab Home Page!

Our research focuses on developing computational and experimental approaches to examine drug-target interactions at the molecular level. Specific techniques include computational methods such as molecular modeling, virtual screening, docking, dynamics, and experimental techniques such as protein x-ray crystallography, enzyme kinetic assays, biophysical assays, and molecular biology techniques. We are using these methods for drug design, resistance prediction, and polymorphism prediction.

  1. Structure-based Drug Design: Structural information by x-ray crystallography for receptors and enzyme targets facilitates rational drug design. We use 3D structures of both protein-based targets and small molecules to design new compounds with improved affinity, efficacy, selectivity, and physiochemical properties. We are currently using these methods to design new inhibitors for HIV and infectious diseases.
  2. Computational Prediction of Drug Resistance: Drug resistance is a major problem for therapeutics used to treat cancer and infectious diseases. Specific mutations or single amino acid changes in the drug target are often responsible for conferring resistance to antivirals, antibiotics, and cancer chemotherapies. Using structure-based knowledge and computational techniques, we can retrospectively examine the effects of drug target mutations on the binding of current therapeutics. Our understanding of resistance mutations will guide the design of new resilient drugs and help predict potential cross-resistance to new inhibitors in development.
  3. Approaches to Examine Polymorphisms in Detoxification Enzymes: Polymorphisms that confer amino acid changes in metabolizing enzymes can affect the rates of biotransformation for several drugs. Such metabolizing enzymes include the CYPS in the cytochrome P450 system, cholinesterases/esterases, and detoxification enzyme GST. A computational and experimental approach can be used to assess the effects of such polymorphisms on the metabolism of various drugs and chemicals. We are currently investigating GST polymorphisms and how amino acid changes in the enzyme may affect detoxification rates.
  4. Drug Design for Polymorphic Enzymes: Drugs targeting polymorphic enzymes such as GSTP may present challenges in treatment efficacy. We are currently evaluating polymorphic drug target GSTP and its effects on orphan drug ezatiostat approved for Myelodysplastic Syndrome (MDS) and related cancers.