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.
Henderson JA, Harris RC, Tsai CC, and Shen J*,
How ligand protonation proton state controls water in protein-ligand binding.
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.
Harris RC, Tsai CC, Ellis CR, Shen J*,
Proton-coupled conformational allostery modulates the inhibitor selectivity for β-secretase.
Ellis CR, Tsai CC, Lin FY, and Shen J*,
Conformational dynamics of cathepsin D and binding to a small-molecule BACE1 inhibitor.
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.