Grossfield Lab

Grossfield Lab Website

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Preprints

  1. Emily Weed-Nichols, James M. Seckler, Paulina M. Getsy, Stephen J. Lewis, Alan Grossfield. A simple theory to explain super-additivity of highly similar drug combinations, bioRxiv 2025.10.27.684841; doi: https://doi.org/10.1101/2025.10.27.684841

  2. Sreyoshi Sur, Alan Grossfield Theoretical estimate of the effective pKa of titratable lipids using continuum electrostatics bioRxiv 2026.04.06.716676; doi: https://doi.org/10.64898/2026.04.06.716676

Papers

  1. Rasouli A, Pickard IV, F. C., Sur, S., Grossfield, A., and Bennet, Mehtap Isik. Essential Considerations for Free Energy Calculations of RNA−Small Molecule Complexes: Lessons from the Theophylline-Binding RNA Aptamer, J. Chem Inf. Model, 2025, 65, 223-239, pdf
  2. Poruthoor, A. J, Sharma, A., and Grossfield, A. Understanding the free-energy landscape of phase separation in lipid bilayers using molecular dynamics. Biophysical J. (2023), 122, 1-16, pdf
  3. Seckler, J. M., Robinson, E. N., Lewis, S. J. & Grossfield, A. Surveying nonvisual arrestins reveals allosteric interactions between functional sites. Proteins Struct Funct Bioinform (2022) doi:10.1002/prot.26413, pdf
  4. Sreyoshi Sur and Alan Grossfield, “Effects of cholesterol on the mechanism of fengycin, a biofungicide“, Biophysical Journal, 2022, 121, 1-12, pdf
  5. Onukwufor, John O., Farooqi, M. Arsalan, Vodičková, Anežka, Koren, Shon, A, Baldzizhar, Aksana, Berry, Brandon, J. Beutner, Gisela, Porter, George A., Belousov, Vsevolod, Grossfield, Alan, Wojtovich, Andrew P., “A reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans“, Nature Communications, 2022, 13, 2403, pdf
  6. Benjamin Gaston, Santhosh M Baby , Walter J May, Alex P Young, Alan Grossfield, James N Bates, James M Seckler , Christopher G Wilson, Stephen J Lewis, “D-Cystine di(m)ethyl ester reverses the deleterious effects of morphine on ventilation and arterial blood gas chemistry while promoting antinociception“, Scientific Reports, 2021, 11;11(1):10038, pdf
  7. Grossfield, A., “How to be a good member of a scientific software community“, Living J. Comp. Mol. Sci., (doi.org/10.33011/livecoms.3.1.1473), 2022 pdf
  8. Romo, T. D., Grossfield, A., and Markelz, A.G., “Persistent Protein Motions in a Rugged Energy Landscape Revealed by Normal Mode Ensemble Analysis“, J. Chem. Inf. Model, 2020, pdf
  9. Maji, D., Grossfield, A., and Kielkopf, C. L., “Structures of SF3b1 reveal a dynamic Achilles heel of spliceosome assembly: Implications for cancer-associated abnormalities and drug discovery“, BBA Gene Regulatory Mechanisms, 2019, 1862, 194440, pdf
  10. Smith, L. G., Tan, Z., Spasic, A., Dutta, D., Salas-Estrada, L. A., Grossfield, A., and Mathews, D. H., “Chemically accurate relative folding stability of RNA hairpins from molecular simulations“, J. Chem. Theor. Comput., 2018, 14, 6598-6612, pdf
  11. Grossfield, A., Patrone, P. N., Roe, D. R., Schultz, A. J., Siderius, D. W., and Zuckerman, D. M., “Best practices for quantification of uncertainty and sampling quality in molecular simulations“, Living Journal of Computational Molecular Science, 2018, 1, 1-24, pdf
  12. Sur, S., Romo, T. D., and Grossfield, A., “Selectivity and mechanism of fengycin, an antimicrobial lipopeptide, from molecular dynamics“, J. Phys. Chem. B, 2018, 122, 2219-2226, pdf
  13. Salas-Estrada, L. A., Leioatts, N., Romo, T. D., and Grossfield, A., “Lipids Alter Rhodopsin Function via Ligand-like and Solvent-like Interactions“, Biophys. J., 2018, 114, 355-367, pdf
  14. Thompson, J. L., Zhao, Y., Stathopulos, P. B., Grossfield, A., and Shuttleworth, T. J.,”Phosphorylation-mediated structural changes within the SOAR domain of STIM1 enable specific activation of distinct Orai channels“, J. Biol. Chem., 2018
  15. Romo, T. D., Lewis, A. K., Braun. A. R., Grossfield, A., and Sachs, J. N., “Minimal Nucleation State of α‐Synuclein Is Stabilized by Dynamic Threonine−Water Networks“, ACS Chemical Neuroscience, 8, 2017, 1859-1864, pdf
  16. Aytenfisu, A. H., Spasic, A., Grossfield, A., Stern, H. A., Mathews, D. H., “Revised RNA dihedral parameters for the Amber force field improve RNA molecular dynamics“, J. Chem. Theor. Comput., 13, 2017, 900-915, pdf
  17. Lin, D., “Generalized and efficient algorithm for computing multipole energies and gradients based on cartesian tensors“, J. Chem. Phys., 143, 2015, 114115, pdf
  18. Lin, D. and Grossfield, A., “Thermodynamics of micelle formation and membrane fusion modulate antimicrobial lipopeptide activity“, Biophysical Journal, 2015, 109, 750-759, pdf
  19. Leioatts, N., Romo, T. D., Danial, S. A., and Grossfield, A., “Retinal conformation changes rhodopsin’s dynamic ensemble“, Biophysical Journal, 2015, 109, 608-617, pdf
  20. Romo, T. D., Leioatts, N. and Grossfield, A., “Lightweight Object Oriented Structure Analysis: Tools for building tools to analyze molecular dynamics simulations“, J. Comput. Chem., 2014, 35, 2305-2318, pdf
  21. Lin, D. and Grossfield, A., “Thermodynamics of Antimicrobial Lipopeptide Binding to Membranes: Origins of Affinity and Selectivity“, Biophysical Journal, 2014, 107, 1862-1872, pdf
  22. Romo, T. D. and Grossfield, A., “How fast is your camera? Time scales for molecular motion and their role in restraining molecular dynamics“, Biophysical Journal, 2014, 106, 2549-2551, pdf
  23. Leioatts, N., Suresh, P., Romo, T. D., and Grossfield, A., “Structure-based simulations reveal concerted dynamics of GPCR activation“, Proteins, 2014, 82, 2538-2551 pdf
  24. Mnpotra, J.S., Qiao, Z., Cai, J., Lynch, D. L., Grossfield, A., Leioatts, N., Hurst, D. P., Pitman, M. C., Song, Z.-H., Reggio, P.H., “Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 Receptor/Gi Protein Complex“, J. Biol. Chem., 2014, 289, 20259-20272
  25. Romo, T. D. and Grossfield, A., “Unknown Unknowns: the Challenge of Systematic and Statistical Error in Molecular Dynamics Simulations“, Biophysical Journal, 2014, 106, 1553-1554, pdf
  26. Leioatts, N., Mertz, B., Martinez-Mayorga, K., Romo, T. D., Pitman, M. C., Feller, S. E., Grossfield, A., Brown, M. F., “Retinal ligand mobility explains internal hydration and reconciles active rhodopsin structures“, Biochemistry, 2014, 53, pp 376–385 pdf
  27. Kimura, T., Vukoti, K., Lynch, D. L., Hurst, D. P, Grossfield, A., Pitman, M. C., Reggio, P. H., Yeliseev, A. A., Gawrisch, K., “Global fold of human cannabinoid type 2 receptor probed by solid-state 13C-, 15N-MAS NMR and molecular dynamics simulations“, Proteins: Struc. Func. Bioinf., 2013, 82, 452-465 pdf
  28. Horn, J. N., Cravens, A. and Grossfield, A., “Interactions between fengycin and model bilayers quantified by coarse-grained molecular dynamics“, Biophysical Journal, 2013, 105, 1612-1623, pdf
  29. Horn, J. N., Romo, T. D., and Grossfield, A., “Simulating the mechanism of antimicrobial lipopeptides with all-atom molecular dynamics”, Biochemistry, 2013, 52, 5604-5610, pdf
  30. Leioatts, N., and Grossfield, A., “Molecular dynamics simulations of membranes and membrane proteins“, in Molecular modeling at the atomic scale – Methods and applications in quantitative biology, ed. Ruhong Zhou, CRC Press, 2014, Ch 9, 243-270
  31. Seckler, J. M., Leioatts, N., Miao, H., and Grossfield, A. “The interplay of structure and dynamics in the function of HIV-1 reverse transcriptase”, Proteins: Struc. Func. Bioinf., 2013, 81, 1792-1801, pdf
  32. Horn, J. N., Kao, T.-C., and Grossfield, A., “Coarse-grained molecular dynamics provides insight into the interactions of lipids and cholesterol with rhodopsin”, in G Protein-Coupled Receptor – Modeling and Simulation, ed. Marta Filizola, Springer, Adv. Exp. Med. Biol., 2014, 796:75–94 pdf
  33. Leioatts, N., Romo, T. D., and Grossfield, A., “Elastic network models are robust to variations in formalism“, J. Chem. Theor. Comput., 2012, 8, 2424-2434 pdf
  34. Olausson, B., Grossfield, A., Pitman, M., Brown, M., Feller, S., Vogel, A., Molecular dynamics simulations reveal specific interactions of post-translational palmitoyl modifications with rhodopsin in membranes, J. Am. Chem. Soc., 2012, 134, 4234-4331 pdf
  35. Horn, J. N., Sengillo, J. D., Lin, D., Romo, T. D., and Grossfield, A., Characterization of a potent antimicrobial lipopeptide via coarse-grained molecular dynamics, Biochim. Biophys. Acta, 2012, 1818, 212-218 pdf
  36. Romo, T. D., and Grossfield, A. Block covariance overlap method and convergence in molecular dynamics simulation, J. Chem. Theor. Comput., 2011, 7, 2464-2472 pdf
  37. Romo, T. D., Bradney, L. A., Greathouse, D. V., and Grossfield, A. Membrane binding of an acyl-lactoferricin B antimicrobial peptide from solid-state NMR experiments and molecular dynamics simulations, Biochim. Biophys. Acta, 2011, 1808, 2019-2030 pdf
  38. Grossfield, A., Recent progress in the study of G protein-coupled receptors with molecular dynamics computer simulations, Biochim. Biophys. Acta, 2011, 1808, 1868–1878, pdf
  39. Romo, T. D. and Grossfield, A., Validating and improving elastic network models using molecular dynamics simulations, Proteins, 2011, 79, 23-34 pdf
  40. Hurst, D. P., Grossfield, A., Lynch, D. L., Feller, S., Romo, T. D., Gawrisch, K., Pitman, M. C., and Reggio, P. H., A lipid pathway for ligand binding is necessary for a cannabinoid G protein-coupled receptor, J. Biol. Chem., 2010, 285, 17954-17964, PMID: 20220143 pdf
  41. Romo, T. D., Grossfield A., and Pitman, M. C. Concerted Interconversion Between Ionic Lock Substates of the b2-Adrenergic Receptor Revealed by Microsecond Time Scale Molecular Dynamics, Biophysical Journal, 2010, 98, 76-84 pdf
  42. Romo, T. D. and Grossfield A., LOOS: An Extensible Platform for the Structural Analysis of Simulations, Proceedings of 31st IEEE-Engineering in Medicine and Biology Conference (2009), 2332-2335 pdf
  43. Grossfield, A., and Zuckerman, D. M. Quantifying uncertainty and sampling quality in biomolecular simulations, Annual Reports in Computational Chemistry, 2009, 5, 23-48, PMC2865156 pdf
  44. Khelashvili, G., Grossfield, A., Feller, S. E., Pitman, M. C., and Weinstein, H. Structural and dynamic effects of cholesterol at preferred sites of interaction with rhodopsin identified from microsecond length molecular dynamics simulations, Proteins: Struc. Func. Bioinf., 2009, 76, 403-417 pdf
  45. Grossfield, A. Implicit modeling of membranes, in “Computational Modeling of Membranes”, ed Scott Feller, Current Topics in Membranes 2008, 60, 131-157 pdf
  46. Grossfield, A., Pitman, M. C., Feller, S. E., Soubias, O., and Gawrisch, K. Internal Hydration Increases during Activation of the G-Protein-Coupled Receptor Rhodopsin, J. Mol. Biol. 2008, 381, 478-486 pdf
  47. Lau, P.-W., Grossfield, A., Feller, S. E., Pitman, M. C., Brown, M. F. Dynamic structure of retinal inverse agonist of rhodopsin probed by molecular dynamics, J. Mol. Biol. 2007, 372, 906-917 pdf
  48. O’Neil, L. L., Grossfield, A., Wiest, O. Computational Investigation of the Base Flipping of the Thymine Dimer in Duplex DNA, J. Phys. Chem. B, 2007, 111, 11843-11849 pdf
  49. Grossfield, A., Feller, S. E., Pitman, M. C. Convergence of molecular dynamics simulations of membrane proteins, Proteins: Struc. Func. Bioinf., 2007, 67, 31-40 pdf
  50. Martínez-Mayorga, K., Pitman, M. C., Grossfield, A., Feller, S. E., and Brown, M. F. Retinal counterion switch mechanism in vision evaluated by molecular simulation, J. Am. Chem. Soc., 2006, 128, 16502-16503 pdf
  51. Jiao, D., King, C., Grossfield, A., Darden T. A., Ren, P. Simulation of Ca2+ and Mg2+ solvation using Polarizable Atomic Multipole Potential, J. Phys. Chem. B, 2006, 110, 18553-18559 pdf
  52. Grossfield, A., Feller, S. E., Pitman, M. C. Contribution of omega-3 fatty acids to the thermodynamics of membrane protein solvation, J. Phys. Chem. B, 2006, 110, 8907-8909 pdf
  53. Grossfield, A., Feller, S. E., Pitman, M. C., A role for direct interactions in the modulation of rhodopsin by omega-3 polyunsaturated lipids, Proc. Nat. Acad. Sci. USA, 2006, 103, 4888-4893 pdf
  54. Fitch, B. G., Rayshubskiy, A., Eleftheriou, M, Ward, T.J.C., Giampapa, M., Zhestkov, Y., Pitman, M. C., Suits, F., Grossfield, A., Pitera, J., Swope, W., Zhou, R., Feller, S., and Germain. R. S., Blue Matter: Strong scaling of molecular dynamics on Blue Gene/L. In V. Alexandrov, D. van Albada, P. Sloot, and J. Dongarra, editors, International Conference on Computational Science (ICCS 2006), volume 3992 of LNCS, pages 846–854. Springer-Verlag, 2006.
  55. Pitman, M. C., Grossfield, A., Suits, F. and Feller, S. E., Role of cholesterol and polyunsaturated lipids in lipid-protein interaction: molecular dynamics simulations of rhodopsin in a realistic membrane environment, J. Am. Chem. Soc., 2005, 127, 4576-4577 pdf
  56. Fitch, B. G., Rayshubskiy, A., Eleftheriou, M, Ward, T.J.C., Giampapa, M., Zhestkov, Y., Pitman, M. C., Suits, F., Grossfield, A., Pitera, J., Swope, W., Zhou, R., Feller, S., and Germain. R. S., Blue Matter: Strong scaling of molecular dynamics on Blue Gene/L. Research Report RC23688, IBM Research Division, 2005.
  57. Grossfield, A. Dependence of ion hydration on the sign of the ion’s charge, J. Chem. Phys., 2005, 122, 024506-10 pdf
  58. Drozdov, A. N., Grossfield, A., and Pappu, R. V., The role of solvent in determining conformational preferences of alanine dipeptide in water, J. Am. Chem. Soc., 2004, 126, 2574-2581 pdf
  59. Grossfield, A., Ren, P., and Ponder, J. W., Single ion solvation thermodynamics from simulations with a polarizable force field, J. Am. Chem. Soc., 2003, 125, 14