One key factor in stabilization of protein drugs in liquid formulations is the choice of appropriate excipients at optimum concentrations that provide extended shelf life while also ensuring highest safety to the patient. Although general principles of stabilization have emerged from the literature over the past decade, the mechanisms by which excipients can improve the stability of a protein d...

PG9 is the founder member of an expanding family of glycan-dependent human antibodies that preferentially bind the HIV (HIV-1) envelope (Env) glycoprotein (gp) trimer and broadly neutralize the virus. Here, we show that a soluble SOSIP.664 gp140 trimer constructed from the Clade A BG505 sequence binds PG9 with high affinity (∼11 nM), enabling structural and biophysical characterizations of the ...

An unusual micelle was discovered in mixtures of the nonionic detergent octaethyleneglycol-mono-n-dodecylether with disaturated phospholipids such as 1,2-dimyristoyl-sn-glycero-3-phosphocholine or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine in water. These mixtures undergo a structural transition upon cooling through the chain-melting temperatures of the respective phospholipids, resulting in t...

Thermodynamic study on the interaction of β-CD with poly ethylene oxide and poly acrylic acid was performed by isothermal titration calorimetry at 298K. when β-CD is added to the interpolymer complex, competition is created between host-guest and Hydrogen bond. Enthalpy of interaction between the β-CD and interpolymer complex was calculated using the extended solvation theory. P=1 Shows that w...

In keeping with the goals of our laboratory, efforts in this thesis are directed towards improving our understanding, and therefore our ability to calculate, the energetics of protein-ligand interactions. Electrostatic contributions to protein-ligand binding events are poorly understood, and underrepresented in data sets used to parameterize the energetics of protein unfolding and binding. Ther...

Isothermal Titration Calorimetry (ITC) provides a sensitive and accurate means by which to study the thermodynamics of RNA folding, RNA binding to small molecules, and RNA-protein interactions. The advent of extremely sensitive instrumentation and the increasing availability of ITC in shared facilities have made it increasingly valuable as a tool for RNA biochemistry. As an isothermal measureme...

Isothermal titration calorimetry (ITC) is a straightforward method to determine basic chemical details of a binding interaction (affinity, thermodynamics and stoichiometry) in a single experiment and under native conditions [1, 2]. Traditionally, ITC experiments are performed using the method of incremental titration, whereby a precise volume of titrant is added to a solution of titrand at disc...

The unfolding enthalpy of the pH 4 molten globule from sperm whale apomyoglobin has been measured by isothermal titration calorimetry, using titration to acid pH. The unfolding enthalpy is close to zero at 20 degrees C, in contrast both to the positive values expected for peptide helices and the negative values reported for holomyoglobin and native apomyoglobin. At 20 degrees C, the hydrophobic...