Assistant Professor of Biochemistry;
B. Sc. 1985, Ph.D. 1988, University of Liverpool.
Tel: (785) 532 5109
Fax: (785) 532 7278
Email: pesmith@ksu.edu
The general focus of the group is the use of computational techniques for the determination of the structure and dynamics of biomolecules. There are many such techniques but our primary tool is molecular dynamics simulations. Biomolecules, be they peptides, proteins or nucleic acids, do not in general adopt a single conformation or structure in solution. Rather, they continually interchange between many low energy conformations only one of which might be biologically important. Using molecular dynamics one can obtain atomic level detail of these structures and the interchange between them which can then be used, often in conjunction with other techniques (nmr, for example), to improve structure based drug design techniques.
More specifically, the group is currently focusing on two areas. 1) The effects of cosolvents on the conformations adopted by peptides in solution. We have been using molecular dynamics to obtain atomic level ``pictures'' of the interactions between cosolvents and peptides. 2) How do proteins fold? An important question which is far from being answered. Conventional explicit solvent molecular dynamics simulations cannot reach the protein folding timescales (ms). We are working on speeding up folding simulation studies by removing the explicit solvent atoms from the simulations, while retaining the effects of solvent (both energetic and dynamical) using effective interaction potentials.
Conformations of Nicotinamide Adenine Dinucleotide (NAD+) in Various
Environments.
P. E. Smith and J. J. Tanner
J. Molec. Recognit. 13:27-34 (2000).
Computer simulation of cosolvent effects on hydrophobic hydration.
P. E. Smith
J. Phys. Chem. B 103:527-534 (1999).
[Abstract] [Article (PDF
format)]
Internal mobility of the basic pancreatic trypsin inhibitor in
solution: A comparison of nmr spin relaxation measurements and molecular
dynamics simulations.
P. E. Smith, R. van Schaik, T. Szyperski, K. Wuethrich, and
W. F. van Gunsteren.
J. Mol. Biol. 246:356-365 (1995).
[Abstract]
Modelling solvent in biomolecular systems.
P. E. Smith and B. M. Pettitt.
J. Phys. Chem. 98:9700-9711 (1994).
[Abstract]
Stochastic dynamics simulations of the alanine dipeptide using a
solvent modified potential energy surface.
P. E. Smith, B. M. Pettitt, and M. Karplus.
J. Phys. Chem. 97:6907-6913 (1993).
[Abstract]