Proteins, both membrane dwelling and soluble, have the remarkable ability to alter their shapes when they interact with other molecules. My work has focused on the ability of one family of membrane proteins and a completely unrelated soluble protein to open and close entrances to cavities and grooves in ways that are fundamental to how they perform their functions. In the first instance, members of the TMEM16 family of Ca2+-activated ion channels and lipid scramblases open a hydrophilic channel or “groove” by which solvent molecules move passively down their electrochemical gradients. However, there is currently ongoing debate over their precise transport mechanisms including whether an open groove is necessary for lipid scrambling, the role of membrane deformation and finally how voltage and lipids modulate TMEM16 activity. I will first describe how I have used atomistic molecular dynamics (MD) simulations to predict new ion-conductive states of the TMEM16A anion channel and show how volage-dependent rotamers of basic residues give rise to current rectification observed in experiments. Then I will describe how I have used an enhanced sampling MD technique to survey 27 TMEM16 scramblase and ion channel structures and determined that these family members do require both an open groove and significant membrane deformation to scramble lipids. My analysis of TMEM16A from both sets of simulations also reveals that lipids partially form the ion conduction pathway without being transported themselves. The latter instance concerns a symmetric light chain antibody dimer that binds heavy atom substituted fluorescent dyes and produces singlet oxygen upon light excitation only when the dye is bound to the protein complex dimer interface. Analogs of the dye molecule give rise to a wide range in the singlet oxygen quantum yields, but it is not understood what mechanism underlies this phenomenon. In the final part of this thesis, I will describe how I have used atomistic MD simulations to discuss how dynamics of the varying part of the dye analogs may be coupled to a conformation change of the protein that widens the dimer cleft, alters solvent exposure to the dye itself and thereby allows excited dye molecules to transfer their energy to molecular oxygen.