Research Expertise and Interest

spectroscopy, molecular structure and dynamics, analytical chemistry, biophysical chemistry, structure and reactivity of biomolecules and biomolecule/water interactions, mass spectrometry, separations, protein conformation, protein and DNA sequencing

Research Description

Professor Williams's research group develops methods, instrumentation, and theory in mass spectrometry, separations, and spectroscopy, with the general goals of understanding the structure, reactivity, and function of biomolecules, including those present in complex mixtures such as cells. Current research problems of interest include:

Protein Conformation and Folding Understanding how proteins fold and the relationship between protein sequence and conformation presents a key challenge in chemistry. The group is investigating the conformation of peptide and protein ions in the gas-phase; both highly compact and fully denatured conformations have been observed. The conformation of these ions with a controlled number of bound water molecules is being investigated to provide a detailed understanding of the role of solvent in protein conformation and folding. A highly sensitive method using capillary electrophoresis combined with mass spectrometry is being developed to obtain information about the sequence and solution-phase conformation of proteins and nucleic acids.

Protein and DNA Sequencing The Williamsí group is developing dissociation methods, including photodissociation and blackbody infrared radiative dissociation, for rapid identification and sequencing of large protein and DNA molecules.

Dynamics of Proton Transfer and Dissociation Reactions Electrostatic interactions in multiply protonated biomolecules play a key role in their structure and function. These interactions also result in unusual ion-molecule charge-transfer and dissociation chemistry that is being explored by experimental methods and by molecular dynamics simulations.

Zwitterion and Salt-bridge Structures Amino acides are zwitterions in aqueous solution within a wide range of pH, whereas their neutral forms are more stable in the gas phase. In the presence of a charge, amino acids can exist as zwitterions in the form of a salt bridge. Salt bridges are often formed in the interior of proteins and strongly influence conformation. Both experiment and theory are used to investigate the structure of amino acids and small peptides as a function of cation size and change, as well as solvation extent to determine the role of electric field and solvent on zwitterion stability.

Non-covalent Complexes Specific non-covalent interactions of biomolecules can be retained in the gas-phase. The binding energy of small complexes can be determined from thermal dissociation measurements. This method is being extended to larger systems, such as enzyme substrate complexes. The combined specificity and sensitivity of this method could greatly facilitate the rapid screening of new drugs.