Publications (2008-2015)

47.  Ellis CR and Shen J*, pH-dependent population shift regulates BACE1 activity and inhibition. 

J Am Chem Soc 137: 9543-9546, 2015.

The aspartyl protease BACE1 is a major pharmaceutical target for treatment of Alzheimer’s disease. Over the past fifteen years, hundreds of inhibitors have been developed some of which have entered clinical trials. However, the fundamental biology of BACE1 including the pH-dependent regulatory mechanism is not well understood. We reported the first molecular simulations to elucidate the mechanism of the pH-dependent enzymatic activity and inhibitor binding of BACE1.

46. Morrow BH, Payne GF, and Shen J*, Stimuli-responsive self-assembly of polysaccharide through a rugged energy landscape. J Am Chem Soc 137: 13024-13030, 2015.

Stimuli-responsive self-assembling materials based on polysaccharide have found a wide range of applications from regenerative medicine to bioelectronics. However, the lack of detailed understanding limits 

technological efforts to access the broad design space. We presented the first all-atom constant pH simulation that describes the simultaneous titration of 240 ionizable sites, while allowing large-scale conformational transitions.

45. Chen W, Shi C, and Shen J*, Nascent beta-hairpin formation of a natively unfolded fragment peptide reveals the role of hydrophobic contacts. Biophys J 109: 630-638, 2015.

44. Chen W, Shi C, MacKerell Jr. AD, and Shen J*, Conformational dynamics of two natively unfolded fragment peptides: Comparison of the AMBER and CHARMM force fields. J Phys Chem B 119: 7902-7910, 2015.

The unfolded states play an important role in protein stability and folding. Here we explored the residual structure in the unfolded NTL9. Interestingly, despite the large number of charged residues, the formation of backbone hydrogen bonds is concomitant with hydrophobic but not electrostatic contacts. The data lends support to a long-standing hypothesis that unfolded states exhibit native-like topology with long-range hydrophobic clusters.

43. Kim E, Xing Y, Cheng Y, Wu H-C, Liu Y, Morrow BH, Ben-Yoav H, Ghodssi R, Rubloff GW, Shen J, Bentley WE, Shi X, and Payne GF*, Chitosan to connect biology to electronics: Fabricating the bio-device interface and communicating across this interface. Polymers 7: 1-46, 2015.

42. Chen W and Shen J*,
Effects of system net charge and electrostatic truncation on all-atom constant pH molecular dynamics.
J Comput Chem 35: 1986-1996, 2014.


41. Morrow BH, Eike DM, Murch BP, Koenig PH, and Shen J*,
Predicting proton titration in cationic micelle and bilayer environments.
J Chem Phys 141: 084714, 2014.


40. Cote Y, Fu IW, Dobson ET, Goldberger JE, Nguyen HD, and Shen J*,
Mechanism of the pH-controlled self-assembly of nanofibers from peptide amphiphiles.
J Phys Chem C 118: 16272-16278, 2014.


39. Chen W, Morrow BH, Shi C, and Shen JK*,
Recent development and application of constant pH molecular dynamics.
Mol Simulat 40: 830-838, 2014.


38. Morrow BH, Koenig PH, and Shen JK*,
Self-Assembly and bilayer-micelle transition of fatty acids studied by replica-exchange constant pH molecular dynamics.
Langmuir 29: 14823-14830, 2013.


37. Chen W, Wallace JA, Yue Z, and Shen JK*,
Introducing titratable water to all-atom molecular dynamics at constant pH.
Biophys J 105: L15-L17, 2013.


36. Morrow BH, Koenig PH, and Shen JK*,
Atomistic simulations of pH-dependent self-assembly of micelle and bilayer from fatty acids.
J Chem Phys 137: 194902, 2012.


35. Wallace JA and Shen JK*,
Charge-leveling and proper treatment of long-range electrostatics in all-atom molecular dynamics at constant pH.
J Chem Phys 137: 184105, 2012.


34. Du, L; King, JB; Morrow, BH; Shen, JK; Miller, AN; Cichewicz, RH*,
An uncommon diaryclopentendione metabolite obtained from a preussia typharum isolate procured using an unconventional cultivation approach.
J Nat Prod 75: 1819-1823, 2012.


33. Yi J*, Morrow BH, Campbell ALO, Shen JK*, and Richter-Addo GB*,
Nitric oxide coupling mediated by iron porphyrins: the N–N bond formation step is facilitated by electrons and a proton.
Chem Commun. 48: 9041-9044, 2012.


32. Wang Y, Shen JK*, Schroeder SJ*,
Nucleotide dynamics at the A-site Cleft in the peptidyl transferase Center of H. marismortui 50S ribosomal subunits.
J Phys Chem Lett 3: 1007-1010, 2012.


31. Wallace JA and Shen JK*,
Unraveling a trap-and-trigger mechanism in the pH-sensitive self-assembly of spider silk proteins.
J Phys Chem Lett 3: 658-662, 2012.


30. Shi C, Wallace JA, and Shen JK*,
Thermodynamic coupling of protonation and conformational equilibria in proteins: theory and simulation.
Biophys J. 102: 1590-1597, 2012.


29. Morrow BH, Wang Y, Wallace JA, Koenig PH, and Shen JK*,
Simulating pH titration of a single surfactant in ionic and nonionic micelles.
J Phys Chem B 115: 14980-14990, 2011.


28. Wallace JA and Shen JK*,
Continuous constant pH molecular dynamics in explicit solvent with pH-based replica exchange.
J Chem Theory Comput 7: 2617-2629, 2011.


27. Wallace JA, Wang Y, Shi C, Pastoor KJ, Nguyen B-L, Xia K, and Shen JK*,
Towards accurate prediction of pKa values for protein internal residues: the importance of conformational relaxation and desolvation energy.
Proteins 79: 3364-3363, 2011.


26. Wang Y, Wallace JA, Koenig PH, and Shen JK*,
Molecular dynamics simulations of ionic and nonionic surfactant micelles with a generalized Born implicit-solvent model.
J Comput Chem 32: 2358, 2011.


25. Alexov E, Mehler EL, Baker NA, Baptista A, Huang Y, Milletti F, Nielsen JE, Farrell D, Carstensen T, Olsson MHM, Shen JK, Warwicker J, Williams S, Word JM,
Progress in the prediction of pKa values in proteins.
Proteins 79: 3260-3275, 2011.


24. Wallace JA and Shen JK*,
Probing the strand orientation and registry alignment in the propagation of amyloid fibrils of Abeta(16-22).
Biochemistry 49:5290-5298, 2010.


23. Shen JK*,
Uncovering specific electrostatic interactions in the denatured states of proteins.
Biophys J 99: 924-932, 2010.


22. Shen JK*,
A method to determine residue-specific denatured-state pKa values from analysis of stability changes in single-mutant cycles.
J Am Chem Soc 132: 7258-7259, 2010.


21. Wallace JA and Shen JK*,
Predicting protein pKa’s with continuous constant pH molecular dynamics.
Methods Enzymol 66: 455-475, 2009.


20. Xu N, Campbell AOL, Powell DR, Khandogin J*, and Richter-Addo GB*,
A stable hyponitrite-bridged iron porphyrin complex.

J Am Chem Soc 130: 16498-16499, 2009.


19. Wickham JW, Halye J, Kashtanov S, Khandogin J, and Rice CV*,
Revisiting magnesium chelation by teichoic acid with phosphorus solid-state NMR and theoretical calculations.
J Phys Chem B 113: 2177-2183, 2009.


18. Qian J, Khandogin J, West AH, Cook P*,
Evidence for a catalytic dyad in the active site of homocitrate synthase from saccaromyces cerevisiae.
Biochemistry 47: 6851-6858, 2009.


17. Khandogin J*,
Modeling protonation equilibria in biological macromolecules.

In Challenges and Advances in Computational Chemistry and Physics, Springer Verlag, Chapter 10, 261-284, 2009.


16. Chen J, Brooks CL III*, and Khandogin J,
Recent advances in implicit solvent based methods for biomolecular simulations.
Curr Opin Struct Biol 18: 140-148, 2008.