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David Minh is a computational chemist who studies protein dynamics and molecular interactions. He develops new methods to predict properties, including binding free energies and signaling efficacies, which could be useful for structure-based drug design.

Education

Ph.D. University of California, San Diego
M.S. University of California, San Diego
B.A. University of California, Berkeley

Research Interests

The research of the David Minh group is in computational chemical biology. That is, we develop and apply computational methods to characterize interactions between small molecules and biological molecules.

More specifically, our current efforts are:

1. Structural mechanisms of activation and strength of signaling through seven transmembrane receptors (7TMRs), traditionally known as G protein coupled receptors (GPCRs), and other signaling proteins. We develop methods that combine physics-based molecular simulation with machine learning to identify intracellular pocket conformations and to compute signaling efficacy. 
2. Computational methods for faster and more accurate binding free energy calculations. Unlike fast molecular docking methods, our new methods consider entropy as well as the enthalpy of binding. We derive new theories that enable computational shortcuts to rigorous binding free energy calculations. We also develop and test computer software that implements the new theory.
3. Techniques to enhance sampling in molecular simulations. Simulations do not need to mimic motion on an atomic scale in order to sample configurations from the proper equilibrium distribution. We are implementing and testing new types of Monte Carlo moves.
4. Chemometric methods for integrating and analyzing measurement data from multiple sources. We developing statistical analysis methods based on Bayesian statistics (the foundation of deep learning) to combine binding-related data from multiple measurements and instruments.
5. Application of molecular modeling to biomedical problems. In collaboration with Oscar Juarez from the biology department, we are currently focusing on modeling metabolic enzymes from pathogenic bacteria. We are studying redox-induced conformational changes and the binding of metabolites and inhibitors. We screen for and optimize new inhibitors as potential antibiotics
    

Professional Affiliations & Memberships

Publications

Nguyen, H. H., Tufts, J., & Minh, D. D. L.*. (2024). On Inactivation of the Coronavirus Main Protease. Journal of Chemical Information and Modeling, acs.jcim.3c01518.

Boby, M. L., Fearon, D., Ferla, M., Filep, M., Koekemoer, L., Robinson, M. C., The COVID Moonshot Consortium‡, Chodera, J. D., Lee, A. A., London, N., Von Delft, A., Von Delft, F., Achdout, H., Aimon, A., Alonzi, D. S., Arbon, R., Aschenbrenner, J. C., Balcomb, B. H., Bar-David, E., Barr, H., Ben-Shmuel, A., Bennett, J., Bilenko, V. A., Borden, B., Boulet, P., Bowman, G. R., Brewitz, L., Brun, J., Bvnbs, S., Calmiano, M., Carbery, A., Carney, D. W., Cattermole, E., Chang, E., Chernyshenko, E., Clyde, A., Coffland, J. E., Cohen, G., Cole, J. C., Contini, A., Cox, L., Croll, T. I., Cvitkovic, M., De Jonghe, S., Dias, A., Donckers, K., Dotson, D. L., Douangamath, A., Duberstein, S., Dudgeon, T., Dunnett, L. E., Eastman, P., Erez, N., Eyermann, C. J., Fairhead, M., Fate, G., Fedorov, O., Fernandes, R. S., Ferrins, L., Foster, R., Foster, H., Fraisse, L., Gabizon, R., García-Sastre, A., Gawriljuk, V. O., Gehrtz, P., Gileadi, C., Giroud, C., Glass, W. G., Glen, R. C., Glinert, I., Godoy, A. S., Gorichko, M., Gorrie-Stone, T., Griffen, E. J., Haneef, A.†, Hassell Hart, S., Heer, J., Henry, M., Hill, M., Horrell, S., Huang, Q. Y. J., Huliak, V. D., Hurley, M. F. D., Israely, T., Jajack, A., Jansen, J., Jnoff, E., Jochmans, D., John, T., Kaminow, B., Kang, L., Kantsadi, A. L., Kenny, P. W., Kiappes, J. L., Kinakh, S. O., Kovar, B., Krojer, T., La, V. N. T., … Zvornicanin, S. N. (2023). Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors. Science, 382, eabo7201.

La, V. N. T., & Minh, D. D. L.*. (2023). Bayesian Regression Quantifies Uncertainty of Binding Parameters from Isothermal Titration Calorimetry More Accurately Than Error Propagation. International Journal of Molecular Sciences, 24, 15074.

La, V. N. T., Nicholson, S.†, Haneef, A.†, Kang, L., & Minh, D. D. L.*. (2023). Inclusion of Control Data in Fits to Concentration–Response Curves Improves Estimates of Half-Maximal Concentrations. Journal of Medicinal Chemistry, 66, 12751–12761.

Nicholson, S.†, Minh, D. D. L., & Eisenberg, R. (2023). H-Bonds in Crambin: Coherence in an α-Helix. ACS Omega, 8, 13920–13934.

Willow, S. Y., Kang, L., & Minh, D. D. L.*. (2023). Learned Mappings for Targeted Free Energy Perturbation between Peptide Conformations. Journal of Chemical Physics, 159, 124104.

Nguyen, T. H., La, V. N. T., Burke, K., & Minh, D. D. L.*. (2022). Bayesian regression and model selection for isothermal titration calorimetry with enantiomeric mixtures. PLoS ONE, 17, e0273656.

Tuz, K., Yuan, M., Hu, Y., Do, T. T. T., Willow, S. Y., DePaolo-Boisvert, J. A., Fuller, J. R., Minh, D. D. L., & Juárez, O. (2022). Identification of the riboflavin cofactor-binding site in the Vibrio cholerae ion-pumping NQR complex: A novel structural motif in redox enzymes. Journal of Biological Chemistry, 298, 102182.

Willow, S. Y., Yuan, M., Juárez, O., & Minh, D. D. L.*. (2021). Electrostatics and water occlusion regulate covalently-bound flavin mononucleotide cofactors of Vibrio cholerae respiratory complex NQR. Proteins: Structure, Function, and Bioinformatics, 89, prot.26158.

Menzer, W. M.†, Xie, B., & Minh, D. D. L.*. (2020). On Restraints in End-Point Protein-Ligand Binding Free Energy Calculations. Journal of Computational Chemistry, 41, 573–586.

Minh, D. D. L.*. (2020). Alchemical Grid Dock (AlGDock): Binding Free Energy Calculations between Flexible Ligands and Rigid Receptors. Journal of Computational Chemistry, 41, 715–730.

Nguyen, T. H., & Minh, D. D. L.*. (2020). Implicit ligand theory for relative binding free energies: II. An estimator based on control variates. Journal of Physics Communications, 4, 115010.

Spiridon, L., Sulea, T. A., Minh, D. D. L., & Petrescu, A. J. (2020). Robosample: Rigid-body molecular simulation based on robot mechanics. BBA - General Subjects, 1864, 129616.

Willow, S. Y., Xie, B., Lawrence, J.†, Eisenberg, R. S., & Minh, D. D. L.*. (2020). On the Polarization of Ligands by Proteins. Physical Chemistry Chemical Physics, 22, 12044–12057.

Xie, B., Yao, Q., Xiang, J., & Minh, D. D. L.*. (2020). A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis. International Journal of Molecular Sciences, 21, 5476.

Fang, X., Osipiuk, J., Chakravarthy, S., Yuan, M., Menzer, W.†, Nissen, D., Liang, P., Raba, D. A., Tuz, K., Howard, A. J., Joachimiak, A., Minh, D. D. L., & Juárez, O. (2019). Conserved residue His-257 of Vibrio cholerae flavin transferase ApbE plays a critical role in substrate binding and catalysis. Journal of Biological Chemistry, 294, 13800–13810.

Nguyen, T. H., Ngo, V., Castro Zerba, J.†, Noskov, S. Y., & Minh, D. D. L.*. (2019). Nonequilibrium path-ensemble averages for symmetric protocols. Journal of Chemical Physics, 151, 194103.

Raba, D. A., Yuan, M., Fang, X., Menzer, W. M.†, Xie, B., Liang, P., Tuz, K., Minh, D. D. L., & Juárez, O. (2019). Role of Subunit D in Ubiquinone-Binding Site of Vibrio cholerae NQR: Pocket Flexibility and Inhibitor Resistance. ACS Omega, 4, 19324–19331.

Xie, B., & Minh, D. D. L.*. (2019). Alchemical Grid Dock (AlGDock) calculations in the D3R Grand Challenge 3. Journal of Computer-Aided Molecular Design, 33, 61–69.

Menzer, W.†, Li, C., Sun, W., Xie, B., & Minh, D. D. L.*. (2018). Simple Entropy Terms for End-Point Binding Free Energy Calculations. Journal of Chemical Theory and Computation, 14, 6035–6049.

Minh, D. D. L.*. (2018). Power transformations improve interpolation of grids for molecular mechanics interaction energies. Journal of Computational Chemistry, 39, 1200–1207.

Nguyen, T. H., & Minh, D. D. L.*. (2018). Implicit ligand theory for relative binding free energies. Journal of Chemical Physics, 148, 104114.

Nguyen, T. H., Rustenburg, A. S., Krimmer, S. G., Zhang, H., Clark, J. D.†, Novick, P. A., Branson, K., Pande, V. S., Chodera, J. D., & Minh, D. D. L.*. (2018). Bayesian analysis of isothermal titration calorimetry for binding thermodynamics. PLoS ONE, 13, e0203224.

Nguyen, T. H., Zhou, H.-X., & Minh, D. D. L.*. (2018). Using the fast fourier transform in binding free energy calculations. Journal of Computational Chemistry, 39, 621–636.

Raba, D. A., Rosas-Lemus, M., Menzer, W. M.†, Li, C., Fang, X., Liang, P., Tuz, K., Minh, D. D. L., & Juárez, O. (2018). Characterization of the Pseudomonas aeruginosa NQR Complex, a Bacterial Proton Pump with Roles in Autopoisoning Resistance. Journal of Biological Chemistry, 293, 15664–15677.

Ren, S., Sun, X., Wang, H., Nguyen, T. H., Sadeghipour, N., Xu, X., Kang, C. S., Liu, Y., Xu, H., Wu, N., Chen, Y., Tichauer, K., Minh, D. D. L., & Chong, H.-S. (2018). Design, Synthesis, and Biological Evaluation of Novel Polyaminocarboxylate Ligand-Based Theranostic Conjugate for Antibody-Targeted Cancer Therapy and Near-Infrared Optical Imaging. ChemMedChem, 13, 2606–2617.

Xie, B., Clark, J. D.†, & Minh, D. D. L.*. (2018). Efficiency of stratification for ensemble docking using reduced ensembles. Journal of Chemical Information and Modeling, 58, 1915–1925.

Onuk, E., Badger, J., Wang, Y. J., Bardhan, J., Chishti, Y., Akcakaya, M., Brooks, D. H., Erdogmus, D., Minh, D. D. L., & Makowski, L. (2017). Effects of Catalytic Action and Ligand Binding on Conformational Ensembles of Adenylate Kinase. Biochemistry, 56, 4559–4567.

Spiridon, L., & Minh, D. D. L.*. (2017). Hamiltonian Monte Carlo with Constrained Molecular Dynamics as Gibbs Sampling. Journal of Chemical Theory and Computation, 13, 4649–4659.

Tuz, K., Li, C., Fang, X., Raba, D. A., Liang, P., Minh, D. D. L., & Juárez, O. (2017). Identification of the Catalytic Ubiquinone-binding Site of Vibrio cholerae Sodium-dependent NADH Dehydrogenase: A NOVEL UBIQUINONE-BINDING MOTIF. Journal of Biological Chemistry, 292, 3039–3048.

Xie, B., Nguyen, T. H., & Minh, D. D. L.*. (2017). Absolute Binding Free Energies between T4 Lysozyme and 141 Small Molecules: Calculations Based on Multiple Rigid Receptor Configurations. Journal of Chemical Theory and Computation, 13, 2930–2944.

Minh, D. D. L., Minh, D. L., & Nguyen, A. L. (2016). Layer Sampling. Communications in Statistics - Simulation and Computation, 45, 73–100.

Nguyen, T. H., & Minh, D. D. L.*. (2016). Intermediate Thermodynamic States Contribute Equally to Free Energy Convergence: A Demonstration with Replica Exchange. Journal of Chemical Theory and Computation, 12, 2154–2161.

Minh, D. D. L., & Minh, D. L. ( (2015). Understanding the Hastings Algorithm. Communications in Statistics - Simulation and Computation, 44, 332–349.

Minh, D. D. L., & Makowski, L. (2013). Wide-angle X-ray solution scattering for protein-ligand binding: Multivariate curve resolution with bayesian confidence intervals. Biophysical Journal, 104, 873–883.

Minh, D. D. L.*. (2012a). Comment on “Transient-state fluctuationlike relation for the driving force on a biomolecule”. Physical Review E, 85, 053103.

Minh, D. D. L.*. (2012b). Implicit ligand theory: Rigorous binding free energies and thermodynamic expectations from molecular docking. Journal of Chemical Physics, 137, 104106.

Minh, D. L., Minh, D. D. L., & Nguyen, A. L. (2012). Regenerative Markov chain Monte Carlo for any distribution. Communications in Statistics - Simulation and Computation, 41, 1745–1760.

Makowski, L., Gore, D. B., Mandava, S., Minh, D. D. L., Park, S., Rodi, D. J., & Fischetti, R. F. (2011). X-ray Solution Scattering Studies of the Structural Diversity Intrinsic to Protein Ensembles. Biopolymers, 95, 531–542.

Minh, D. D. L.*, & Chodera, J. D. (2011). Estimating equilibrium ensemble averages using multiple time slices from driven nonequilibrium processes: Theory and application to free energies, moments, and thermodynamic length in single-molecule pulling experiments. Journal of Chemical Physics, 134, 024111.

Minh, D. D. L.*, & Vaikuntanathan, S. (2011). Density-dependent analysis of nonequilibrium paths improves free energy estimates II. A Feynman-Kac formalism. Journal of Chemical Physics, 134, 034117.

Nilmeier, J. P., Crooks, G. E., Minh, D. D. L., & Chodera, J. D. (2011). PNAS Plus: Nonequilibrium candidate Monte Carlo is an efficient tool for equilibrium simulation. Proceedings of the National Academy of Sciences of the United States of America, 108, E1009–E1018.

Minh, D. D. L.*. (2010). Optimized replica gas estimation of absolute integrals and partition functions. Physical Review E, 82, 31132.

Qin, S. B., Minh, D. D. L., McCammon, J. A., & Zhou, H.-X. X. (2010). Method to Predict Crowding Effects by Postprocessing Molecular Dynamics Trajectories: Application to the Flap Dynamics of HIV-1 Protease. Journal of Physical Chemistry Letters, 1, 107–110.

Minh, D. D. L.*. (2009). Density-dependent analysis of nonequilibrium paths improves free energy estimates. Journal of Chemical Physics, 130, 204102.

Minh, D. D. L., & Adib, A. B. (2009). Path integral analysis of Jarzynski’s equality: Analytical results. Physical Review E, 79, 021122.

Minh, D. D. L.*, & Chodera, J. D. (2009). Optimal estimators and asymptotic variances for nonequilibrium path-ensemble averages. Journal of Chemical Physics, 131, 134110.

Makowski, L., Rodi, D. J., Mandava, S., Minh, D. D. L., Gore, D. B., & Fischetti, R. F. (2008). Molecular crowding inhibits intramolecular breathing motions in proteins. Journal of Molecular Biology, 375, 529–546.

Minh, D. D. L., & Adib, A. B. (2008). Optimized free energies from bidirectional single-molecule force spectroscopy. Physical Review Letters, 100, 180602.

Minh, D. D. L.*, & McCammon, J. A. (2008). Springs and speeds in free energy reconstruction from irreversible single-molecule pulling experiments. Journal of Physical Chemistry B, 112, 5892–5897.

Amaro, R. E., Minh, D. D. L., Cheng, L. S., Lindstrom William M, J., Olson, A. J., Lin, J.-H. H., Li, W. W., & McCammon, J. A. (2007). Remarkable loop flexibility in avian influenza N1 and its implications for antiviral drug design. Journal of the American Chemical Society, 129, 7764–7765.

Minh, D. D. L.*. (2007). Multidimensional Potentials of Mean Force from Biased Experiments along a Single Coordinate. Journal of Physical Chemistry B, 111, 4137–4140.

Minh, D. D. L.*, Hamelberg, D., & McCammon, J. A. (2007). Accelerated entropy estimates with accelerated dynamics. Journal of Chemical Physics, 127, 154105.

Minh, D. D. L.*. (2006). Free-energy reconstruction from experiments performed under different biasing programs. Physical Review E, 74, 61120.

Minh, D. D. L.*, Chang, C.-e. A., Trylska, J., Tozzini, V., & McCammon, J. A. (2006). The influence of macromolecular crowding on HIV-1 protease internal dynamics. Journal of the American Chemical Society, 128, 6006–6007.

Minh, D. D. L.*, Bui, J. M., Chang, C.-e., Jain, T., Swanson, J. M. J., & McCammon, J. A. (2005). The Entropic Cost of Protein-Protein Association: A Case Study on Acetylcholinesterase Binding to Fasciculin-2. Biophysical Journal, 89, L25–L27.

Expertise

• Computational Chemical Biology and Structure-Based Drug Design
• Theoretical Chemistry, especially Statistical Mechanics
• Biophysical Chemistry