Dr. Paul Smith

Paul E. Smith

Associate Professor of Chemistry

Computer simulation of the structure and dynamics of peptides, proteins and nucleic acids. Cosolvent effects on peptides and proteins. Modeling of opioid peptides and their receptors.

B.S. 1985, University of Liverpool

Ph.D. 1988, University of Liverpool

Postdoctoral Associate, University of Houston (1989-1991), Eidgenoessische Technische Hochschule, Zurich (1992-1993)

Phone: 785-532-5109

Fax: 785-532-6666

Email: pesmith@ksu.edu

Office: 112 King Hall

The general focus of the group is the study of the effects of solvent and cosolvents on the structure and dynamics of biomolecules in solution. Our main tool is molecular dynamics simulations which are used to provide atomic level detail concerning the properties of these molecules. In particular, we are attempting to: i) extend the application of computer simulations to more physiologically relevant conditions; ii) characterize the denatured state of proteins as produced by different cosolvents (denaturants); and iii) to understand the structure and folding of peptides and proteins in solution.

Improved force field parameters
By simulating the motion of molecules using a computer one can investigate the interactions between molecules at the atomic level. This can provide new and interesting data not available by experiment. Molecular dynamics simulation can be applied to investigate many diverse phenomena. However, a key to their success is a correct modeling of the interaction energy (or force field) between molecules. We are currently attempting to improve the parameters used in molecular dynamics simulations in an effort to provide more accurate properties of a variety of systems. New force fields have been developed for mixtures of water with urea, acetone, sodium chloride, methanol, and guanidium chloride, and are now being extended to cover other salts, amides and alcohols.

Peptide folding
Using simulations we have been studying the mechanism by which peptides fold to adopt stable structures in solution. Our current studies have focused on the formation of hairpins. Using computer simulations we have been able to observe hairpin formation and are now investigating the factors that stabilize the final hairpin structure, and the role of the unfolded state in hairpin stability.

Opioid peptides and delta-opioid receptor modeling
Opioids are small peptides that play a major role in our response to pain. The design of improved and non addictive new pain killing drugs depends on an understanding of the interaction between opioids and their receptor. The exact site of opioid peptide binding to the receptor is unknown. We have recently developed a model for the delta-opioid receptor which can be used to probe the interactions between potential drug molecules and the receptor.

d-opioid receptor Model of the delta-opioid receptor in a lipid bilayer.

Selected Publications

The role of the unfolded state in hairpin stability. Hongxing Lei and Paul E. Smith. Biophysical J., 85:3513-3520, 2003.

A Combined Simulation and Kirkwood-Buff Approach to Quantify Cosolvent Effects on the Conformational Preferences of Peptides in Solution. Mahalaxmi Aburi and Paul E. Smith. J. Phys. Chem. B, 108:7382-7388, 2004.

A Kirkwood-Buff derived force field for the simulation of aqueous guanidinium chloride solutions. Samantha Weerasinghe and Paul E. Smith. J. Chem. Phys., 121:2180-2186, 2004.

Modeling and Simulation of the Human Delta Opioid Receptor. Mahalaxmi Aburi and Paul E. Smith. Protein Science, 13:1997-2008, 2004.

Complete Publications List