Enzyme Dynamics and Inhibition 

We demonstrated that CpHMD can be used to understand the pH-dependent activity of enzymes and to refine our understanding of protein-ligand binding as well as free energy calculations. The latter study led to the discovery of the first allosteric mechanism underlying pH-dependent selectivity of an enzyme.

 

Tsai CC, Yue Z, and Shen J*, 

How electrostatic coupling enables conformational plasticity in a tyrosine kinase.

J Am Chem Soc, ASAP, 2019.

Liu R, Yue Z, Tsai CC, and Shen J*, 

Assessing lysine and cysteine reactivities for designing targeted covalent kinase inhibitors.

J Am Chem Soc 141: 6553-6560, 2019. 

Henderson JA, Harris RC, Tsai CC, and Shen J*,  

How ligand protonation proton state controls water in protein-ligand binding. 

J Phys Chem Lett 9: 5440-5444, 2018.

Huang YD, Yue Z, Tsai CC, Henderson JA, and Shen J*,  Predicting catalytic proton donors and nucleophiles in enzymes: how adding dynamics helps elucidate the structure-function relationships. 

J Phys Chem Lett 9: 1179-1184, 2018.

Harris RC, Tsai CC, Ellis CR, Shen J*,

Proton-coupled conformational allostery modulates the inhibitor selectivity for β-secretase.

J Phys Chem Lett 8: 4832-4837, 2017.

 

Ellis CR, Tsai CC, Lin FY, and Shen J*,

Conformational dynamics of cathepsin D and binding to a small-molecule BACE1 inhibitor.

J Comput Chem 38: 1260-1269, 2017.

Ellis CR, Tsai CC, Hou XJ, and Shen J*,
Constant pH molecular dynamics reveals pH-modulated binding of two small-molecule BACE1 inhibitors.
J Phys Chem Lett 7: 944-949, 2016.

 

Ellis CR and Shen J*,
pH-dependent population shift regulates BACE1 activity and inhibition.
J Am Chem Soc 137: 9543-9546, 2015.