Web Publications

Selected Publications (Full Publication List via Google Scholar)

  • Fenley*, A.T., Killian*, B.J., Hnizdo, V., Fedorowicz, Sharp, D.S., and Gilson, M.K., Correlation as a Determinant of Configurational Entropy in Supramolecular and Protein Systems. J. Phys. Chem. B, 118(28): 6447-6455, 2014. LINK
  • Muddana, H.S., Sapra, N.V., Fenley, A.T., and Gilson, M.K., The SAMPL4 hydration challenge: evaluation of partial charge sets with explicit-water molecular dynamics simulations. J. Comput.-Aided Mol. Des. 28(3): 277-287, 2014. LINK
  • Muddana, H.S., Fenley, A.T., Mobley, D.L., and Gilson, M.K., The SAMPL4 host-guest blind prediction challenge: an overview. J. Comput.-Aided Mol. Des. 28(4): 305-317, 2014. LINK
  • Velez-Vega, C. and Gilson, M.K., Overcoming dissipation in the calculation of standard binding free energies by ligand extraction. J. Comput. Chem. 34:2360-2371, 2013. [Introduces Attach-Pull-Release method for using potential of mean force calculations to compute standard free energy of binding with molecular dynamics simulations.]
  • Muddana, H.S. and Gilson, M.K. Calculation of Host-Guest Binding Affinities Using a Quantum-Mechanical Energy Model. J. Chem. Theory Comput. 8(6):2023-2033, 2012. [Introduces mining minima binding free energy calculations using quantum chemistry instead of force fields.]
  • Fenley, A.T., Muddana, H.S., and Gilson, M.K. Entropy-enthalpy transduction caused by conformational shifts can obscure the forces driving protein-ligand binding. Proc. Natl. Acad. Sci. U.S.A. 109(49):20006-11, 2012. [Provides evidence, from a 1 ms molecular dynamics simulation, that protein-water systems transition among states of similar free energy but disparate enthalpy and entropy, and argues that such transitions may explain common thermodynamic puzzles.] LINK
  • Nguyen, C.N., Young, T.K., and Gilson, M.K. Grid inhomogeneous solvation theory: hydration structure and thermodynamics of the miniature receptor cucurbit[7]uril. J. Chem. Phys.137(4):044101, 2012. [Introduces theory and method of a new technique for extracting information about the structure and thermodynamics of binding-site water from simulations. Method is demonstrated with application to the ultra-high affinity synthetic receptor cucurbit[7]uril.]
  • Muddana, H.S., Varnado, D., Bielawski, C.W., Urbach, A.R., Isaacs, L., Geballe, M.T., and Gilson, M.K. Blind prediction of host-guest binding affinities: A new SAMPL3 challenge. J. Comput. Aided Mol. Des., 26:475-487, 2012. [Introduces host-guest systems as a basis for rigorous testing of computational models of binding.]
  • Nicola,G., Liu,T., and Gilson,M.K. Public domain databases for medicinal chemistry, J. Med. Chem. 55:6987-7002, 2012. [Reviews the increasingly powerful information resources available to inform and guide medicinal chemistry, focusing on PubChem, ChEMBL, and our lab's BindingDB.]
  • Zhou, H-X. and Gilson, M.K. Theory of free energy and entropy in noncovalent binding. Chem. Rev. 109:4092-4107, 2009. [A didactic review which tries to provide intuitive insight into basic issues in the theory and calculation of binding affinities, including various ways of looking at changes in entropy.]
  • Rekharsky, M.V., Mori, T., Yang, C., Ko, Y.H., Selvapalam, N., Kim, H., Sobrasingh, D., Kaifer, A.E., Liu, S., Isaacs, L.*, Chen, W., Moghaddam, S., Gilson, M.K.*, Kim, K.*, and Inoue, Y.* A synthetic host-guest system achieves avidin-biotin affinity by overcoming enthalpy-entropy compensation.Proc. Nat. Acad. Sci. USA. 104: 20737-20742, 2007. [A miniature receptor-ligand (host-guest) pair with a binding affinity on par with that of biotin with avidin!]
  • Killian, B.J., Kravitz, J.Y., and Gilson, M.K. Extraction of configurational entropy from molecular simulations via an expansion approximation. J. Chem. Phys. 127:024107, 2007. [First application of the mutual information expansion to extract entropy estimates from molecular simulations. Also goes into the theoretical background.]
  • Gilson, M.K. and Zhou, H-X. Calculation of protein-ligand binding affinities. Ann. Rev. Biophys. Biomol. Struct. 2007. 36:21-42, 2007. [A relatively chatty overview of various approaches to estimating protein-ligand binding affinities, from docking and knowledge-based methods to high-end physics-based methods using quantum mechanics and atomistic simulations.]
  • Chen, W., Chang, C., and Gilson, M.K. Calculation of cyclodextrin binding affinities: Energy, entropy and implications for drug design. Biophys. J. 87:3035-3049, 2004. [With the following paper, introduces our lab's mining minima method, and uses it to study cyclodextrin-drug binding.]
  • Chang, C. and Gilson, M.K. Free energy, entropy, and induced fit in host-guest recognition. J. Am. Chem. Soc. 126:13156-13164, 2004. [First description and use of mining minima technology, and some interesting results!]
  • Gilson, M.K., Given, J.A., Bush, B., and McCammon, J.A. The statiscal-thermodynamic basis for computation of binding affinities. A critical review. Biophys. J. 72:1047-1069, 1997. [Perhaps the first paper to give a rigorous formula for the standard free energy of binding in terms of partition functions. Introduces the Double Decoupling method of computing binding affinities, provides theoretical grounding for the use of continuum solvent models in binding calculations, and clarifies issues relating to changes in rotational and translational entropy on binding.]
  • Antosiewicz,J., McCammon,J.A. and Gilson,M.K. Prediction of pH-dependent properties of proteins. (1994) J. Molec. Biol. 238: 415-436. [Uses Poisson-Boltzmann electrostatics to compute protein pKas and discovered that accuracy was greatest when we raised the protein dielectric constant to the arguably nonphysical value of 20. Also introduced the use of null models, drawn from biostatistics, to the validation of computational chemistry methods.]
  • Gilson,M.K., Davis,M.E., Luty,B.A. and McCammon,J.A. (1993) Computation of electrostatic forces on solvated molecules using the Poisson-Boltzmann equation. J. Phys. Chem. 97:3591-3600. [Provides theory and method for computing electrostatic forces on molecules in solution from continuum electrostatics models.  A key insight is that the high-dielectric solvent feels a force pulling into regions of high electrical field.]
  • Gilson,M.K. (1993) Multiple-site titration and molecular modeling: Two rapid methods for computing energies and forces for ionizable groups in proteins. Proteins: Structure, Function and Genetics 15:266-282. [Developed statistical thermodynamics of protonation equilibria in proteins, and an approximate method for solving the problem in the context of continuum electrostatics.]
  • Gilson,M.K. and Honig,B. (1991) The inclusion of electrostatic hydration energies in molecular mechanics calculations. J. Computer-Aided Drug Design 5:5-20. [Shows how detailed solutions of the continuum electrostatics field equations can be approximated by a computationally fast solvent-displacement function, where an atom approaching a charge raises the energy approximation as 1/r^4; and notes that the degree to which a charged atom is desolvated would modulate its interactions with other charged atoms. Basis of the Generalized Born approach.]
  • Gilson,M.K. and Honig,B. (1988) Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies, and conformational analysis. Proteins: Structure, Function, and Genetics 4:7-18. [Shows how finite-difference solutions of the linearized Poisson-Boltzmann equation can be used to model the full effects of the high dielectric solvent: not just charge-charge screening, but also the desolvation of charges on binding or folding. Groundwork for continuum models of solvation.]
  • Gilson,M.K. and Honig,B. (1987) Calculation of electrostatic potentials in an enzyme active site.Nature 330: 84-86. [Tests continuum electrostatics by using finite-difference solutions of the linearized Poisson-Boltzman equation to compute experimentally determined pKa shifts of a catalytic histidine, due to charge-altering mutants about 10 Angstroms away.]
  • Gilson,M.K. and Honig,B. (1986) The dielectric constant of a folded protein. Biopolymers 25:2907-2119. [First calculation of the dielectric constant of a protein. Uses Kirkwood-Frohlich theory, with normal mode calculations of an alpha-helix to estimate dipole-moment fluctuations.]


  • US Patent 8,140,268. Computational method for drug discovery and receptor design. Inventor: Michael Jason Potter, Gilson Rodman, Hillary Sue, Michael Kenneth Gilson. 2009.
  • US Patent 6,970,791. Tailored user interfaces for molecular modeling. Michael Jason Potter, Hillary Sue Rodman Gilson and Michael Kenneth Gilson. 2005.