David Minh

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

American Chemical Society

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. https://doi.org/10.1021/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. https://doi.org/10.1126/science.abo7201

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. https://doi.org/10.3390/ijms242015074

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. https://doi.org/10.1021/acs.jmedchem.3c00107

Nicholson, S.†, Minh, D. D. L., & Eisenberg, R. (2023). H-Bonds in Crambin: Coherence in an α-Helix. ACS Omega, 8, 13920–13934. https://doi.org/10.1021/acsomega.3c00181

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. https://doi.org/10.1063/5.0164662

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. https://doi.org/10.1371/journal.pone.0273656

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. https://doi.org/10.1016/j.jbc.2022.102182

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. https://doi.org/10.1002/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. https://doi.org/10.1002/jcc.26119

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. https://doi.org/10.1002/jcc.26036

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. https://doi.org/10.1088/2399-6528/abcbac

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. https://doi.org/10.1016/j.bbagen.2020.129616

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. https://doi.org/10.1039/d0cp00376j

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. https://doi.org/10.3390/ijms21155476

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. https://doi.org/10.1074/jbc.RA119.008261

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. https://doi.org/10.1063/1.5121306

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. https://doi.org/10.1021/acsomega.9b02707

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. https://doi.org/10.1007/s10822-018-0143-9

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. https://doi.org/10.1021/acs.jctc.8b00418

Minh, D. D. L.*. (2018). Power transformations improve interpolation of grids for molecular mechanics interaction energies. Journal of Computational Chemistry, 39, 1200–1207. https://doi.org/10.1002/jcc.25180

Nguyen, T. H., & Minh, D. D. L.*. (2018). Implicit ligand theory for relative binding free energies. Journal of Chemical Physics, 148, 104114. https://doi.org/10.1063/1.5017136

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. https://doi.org/10.1371/journal.pone.0203224

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. https://doi.org/10.1002/jcc.25139

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. https://doi.org/10.1074/jbc.RA118.003194

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. https://doi.org/10.1002/cmdc.201800598

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. https://doi.org/10.1021/acs.jcim.8b00314

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. https://doi.org/10.1021/acs.biochem.7b00351

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. https://doi.org/10.1021/acs.jctc.7b00570

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. https://doi.org/10.1074/jbc.M116.770982

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. https://doi.org/10.1021/acs.jctc.6b01183

Minh, D. D. L., Minh, D. L., & Nguyen, A. L. (2016). Layer Sampling. Communications in Statistics - Simulation and Computation, 45, 73–100. https://doi.org/10.1080/03610918.2013.854907

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. https://doi.org/10.1021/acs.jctc.6b00060

Minh, D. D. L., & Minh, D. L. ( (2015). Understanding the Hastings Algorithm. Communications in Statistics - Simulation and Computation, 44, 332–349. https://doi.org/10.1080/03610918.2013.777455

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. https://doi.org/10.1016/j.bpj.2012.12.019

Minh, D. D. L.*. (2012a). Comment on “Transient-state fluctuationlike relation for the driving force on a biomolecule”. Physical Review E, 85, 053103. https://doi.org/10.1103/PhysRevE.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. https://doi.org/10.1063/1.4751284

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. https://doi.org/10.1080/03610918.2011.615433

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. https://doi.org/10.1002/bip.21631

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. https://doi.org/10.1063/1.3516517

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. https://doi.org/10.1063/1.3541152

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. https://doi.org/10.1073/pnas.1106094108

Minh, D. D. L.*. (2010). Optimized replica gas estimation of absolute integrals and partition functions. Physical Review E, 82, 31132. https://doi.org/10.1103/PhysRevE.82.031132

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. https://doi.org/10.1021/jz900023w

Minh, D. D. L.*. (2009). Density-dependent analysis of nonequilibrium paths improves free energy estimates. Journal of Chemical Physics, 130, 204102. https://doi.org/10.1063/1.3139189

Minh, D. D. L., & Adib, A. B. (2009). Path integral analysis of Jarzynski’s equality: Analytical results. Physical Review E, 79, 021122. https://doi.org/10.1103/PhysRevE.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. https://doi.org/10.1063/1.3242285

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. https://doi.org/10.1016/j.jmb.2007.07.075

Minh, D. D. L., & Adib, A. B. (2008). Optimized free energies from bidirectional single-molecule force spectroscopy. Physical Review Letters, 100, 180602. https://doi.org/10.1103/PhysRevLett.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. https://doi.org/10.1021/jp0733163

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. https://doi.org/10.1021/ja0723535

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. https://doi.org/10.1021/jp068656n

Minh, D. D. L.*, Hamelberg, D., & McCammon, J. A. (2007). Accelerated entropy estimates with accelerated dynamics. Journal of Chemical Physics, 127, 154105. https://doi.org/10.1063/1.2794754

Minh, D. D. L.*. (2006). Free-energy reconstruction from experiments performed under different biasing programs. Physical Review E, 74, 61120. https://doi.org/10.1103/PhysRevE.74.061120

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. https://doi.org/10.1021/ja060483s

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. https://doi.org/10.1529/biophysj.105.069336

Expertise

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