Biological targets: Our current focuses are on protein kinases and phosphatases.
Incorporation of protein flexibility in molecular docking: In addition to performing molecular dynamics simulation to generate ensembles of protein structures for molecular docking, we have also developed simulated annealing cycling protocols to faciliate flexible ligand-flexible protein docking. References:
Z. Huang & C.F. Wong, "Docking Flexible Peptide to Flexible Protein by Molecular Dynamics Using Two Implicit-Solvent Models: An Evaluation in Protein Kinase and Phosphatase Systems", J. Phys. Chem. B, 113 (2009) 14343-14354.
Z. Huang & C.F. Wong, "Conformational Selection of Protein Kinase A Revealed by Flexible-Ligand Flexible-Protein Docking", J. Comput. Chem. 30 (2009) 631-644.
C.F. Wong, “Flexible Ligand-Flexible Protein Docking in
Protein Kinase Systems”, Biochim Biophys Acta., 1784 (2008)
244-251.
Z. Huang, C.F. Wong & R. Wheeler, "Flexible
Protein-Flexible
Ligand Docking with Disrupted Velocity Simulated Annealing", Proteins:
Structure, Function, Bioinformatics, 7 (2008) 440-454.
Computational models for calculating binding affinity to aid lead optimization: Recently, we have combined the Poisson-Boltzmann solver in the University of Houston Brownian Dynamics Program with two quantum mechanical codes (PWSCF and SIESTA) to faciliate these calculations. References:
B. Zhou, M. Agarwal & C.F. Wong, “Variable Atomic
Radii
for Continuum-Solvent Electrostatics Calculation”, J. Chem.
Phys. 129 (2008)
014509.
M. Wang, C. F. Wong, J. Liu & P. Zhang,
"Efficient Quantum Mechanical Calculation of Solvation Free Energies
Based on Density Functional Theory, Numerical Atomic Orbitals and
Poisson–Boltzmann Equation", Chem. Phys. Lett., 442 (2007)
464-467.
M. Wang & C.F. Wong, "Rank-ordering Protein-Ligand
Binding
Affinity by a QM/MM/PBSA Model", J. Chem. Phys., 126 (2007) 026101.
M. Wang & C.F. Wong, “Calculation
of Solvation Energy from Quantum Mechanical Charge Density and
Continuum
Dielectric Theory”, J. Phys. Chem. A, 110 (2006) 4873-4879.
Pathway models for drug design: In addition to simulating the interaction of drugs or drug candidates with their direct biological targets, we are also simulating their effects on other molecular components of a signaling pathway. Reference:
M. Goyal, M. Rizzo, F. Schumacher & C.F. Wong, "Beyond Thermodynamics: Drug Binding Kinetics Could Influence Epidermal Growth Factor Signaling", J. Med. Chem., 52 (2009) 5582-5585.
Simulation of the kinetics of drug-binding to protein targets: As the kinetics of drug-binding, in addition to thermodynamics, might also determine the effectiveness of therapeutic drugs, we are performing simulation to study the kinetics of drug binding to biological targets. Reference:
Z. Huang & C.F. Wong, "A Mining-Minima Approach to
Exploring
the Docking Pathways of p-Nitrocatechol Sulfate to YopH", Biophys. J.,
83 (2007) 4141-4150.