David Minh

  • Robert E. Frey, Jr. Endowed Chair in Chemistry
  • Associate Professor of Chemistry
  • Associate Director, Center for Interdisciplinary Scientific Computation (CISC)


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. 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.
  2. 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.
  3. Chemometric methods for integrating and analyzing measurement data from multiple sources. We are writing statistical analysis packages based on Bayesian statistics (the foundation of deep learning) to combine binding-related data from multiple measurements and instruments. The programs will also propose new experiments that maximize information gain.
  4. 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 plan to screen for and optimize new inhibitors as potential antibiotics.


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.

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. & Juarez, O. (2019). Kinetic and Reaction Mechanism of Vibrio cholerae Flavin Transferase ApbE: Role of Conserved Histidine 257 in 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.†, Liang, P., Tuz, K., Minh, D. D. L. & Juarez, O. (2019). Role of subunit D in the 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, 104114.4

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. 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 DDL, Minh DL, Nguyen L. Layer Sampling, Commun Stat Simulat Comput, in press. doi: 10.1080/03610918.2013.854907

Minh DDL, Minh DL. Understanding the Hastings Algorithm, Commun Stat Simulat Comput, 44:2, 332-349 (2015). doi: 10.1080/03610918.2013.777455

Minh DDL, Makowski L. Wide-angle X-ray solution scattering for protein-ligand binding: Multivariate curve resolution with Bayesian confidence intervals. Biophysical Journal, 104: 873-883 (2013). doi: 10.1016/j.bpj.2012.12.019

Minh DDL. Implicit Ligand Theory: Rigorous binding free energies and thermodynamic expectations from molecular docking. J Chem Phys, 137: 104106 (2012). doi:10.1063/1.4751284

Nilmeier JP, Crooks GE, Minh DDL, Chodera JD. Nonequilibrium candidate Monte Carlo is an efficient tool for equilibrium simulation, Proc Natl Acad Sci USA, 108(45):E1009-1018 (2011). doi:10.1073/pnas.1106094108

Minh DDL, Vaikuntanathan S. Density-Dependent Analysis of Nonequilibrium Paths Improves Free Energy Estimates II. A Feynman-Kac Formalism. J Chem Phys, 134(3): 034117 (2011). doi:10.1063/1.3541152

Minh DDL, Chodera JD. 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. J Chem Phys, 134(2): 024111 (2011). doi:10.1063/1.3516517

Minh DDL. Optimized replica gas estimation of absolute integrals and partition functions. Phys Rev E, 82(3): 031132 (2010). doi:10.1103/PhysRevE.82.031132

Minh DDL, Chodera JD. Optimal estimators and asymptotic variances for nonequilibrium path-ensemble averages. J Chem Phys, 131(13): 134110 (2009). doi:10.1063/1.3242285

Minh DDL. Density-Dependent Analysis of Nonequilibrium Paths Improves Free Energy Estimates. J Chem Phys, 130(20): 204102 (2009). doi:10.1063/1.3139189

Minh DDL, Adib AB. Path integral analysis of Jarzynski's equality: Analytical results. Phys Rev E, 79(2): 021122 (2009). doi: 10.1103/PhysRevE.79.021122

Minh DDL, Adib AB. Optimized free energies from bidirectional single-molecule force spectroscopy. Phys Rev Lett, 100(18): 180602 (2008). doi:10.1103/PhysRevLett.100.180602

Amaro R, Minh DDL, Cheng L, Lindstrom WM, Olson AJ, Lin JH, Olson AJ, McCammon JA. Remarkable Loop Flexibility in Avian Influenza N1 and its Implications for Antiviral Drug Design. J Am Chem Soc, 129(25):7764-7765 (2007). doi:10.1021/ja0723535

Minh DDL. Free Energy Reconstruction from Experiments Performed Under Different Biasing Programs. Phys Rev E, 74(6): 061120 (2006). doi:10.1103/PhysRevE.74.061120

Minh DDL, Chang CE, Trylska J, Tozzini V, and McCammon JA. The influence of macromolecular crowding on HIV-1 protease internal dynamics. J Am Chem Soc, 128(18): 6006-6007 (2006). doi:10.1021/ja060483s

Minh DDL, Bui JM, Chang CE, Jain T, Swanson JM, McCammon JA. The entropic cost of protein-protein association: a case study on acetylcholinesterase binding to fasciculin-2. Biophys J, 89(4):L25-7 (2005). doi:10.1529/biophysj.105.069336


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