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 interactions between peptides and proteins in solution.
Major areas of current interest include:
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 various solutes characteristic of functional groups common in amino acids. The force fields are specifically designed to reproduce the experimental Kirkwood-Buff (KB) integrals and hence provide a realistic description of the solution distributions and thermodynamics (KBFF). Our future aim is a full protein force field.
KB theory is an exact theory of solution mixtures which relates solution distributions to the corresponding thermodynamics. Recently, there has been a renewed interest in using KB theory to understand biological systems. We have been involved in developing the equations, approaches, and simple models for these types of applications.
Using computer simulations and the theory developed above we are starting to perform simulations of peptides at finite concentrations in an effort to understand the factors that give rise to peptide aggregation. We also interested in the use of cosolvents to manipulate the aggregation process.
Modelling Biomolecule and Nanoparticle Complexes
MspA is a bacterial porin which displays remarkable thermal stability and will insert into virtually any membrane. MspA can also complex a variety of molecules including spherical Au nanoparticles of 4 nm in diameter. We have been simulating the MspA octamer in lipid bilayers to understand the structure and dynamics, and protonation state, of this porin. Our future studies will investigate the properties of MspA complexed with Au nanoparticles as potential cancer therapeutics.
MspA bound Au Nanoparticles
Myungshim Kang and Paul E. Smith, Kirkwood-Buff Theory of Four and Higher Component Mixtures. J. Chem. Phys., 128: 244511, 2008.
Paul E. Smith and Robert M. Mazo, On the Theory of Solute Solubility in Mixed Solvents. J. Phys. Chem. B, 112:7875-7884, 2008.
Feng Chen and Paul E. Smith, Theory and computer simulation of solute effects on the surface tension of liquids. J. Phys. Chem. B, 2008, in press
Raj Kumar Dani, Myungshim Kang, Mausam Kalita, Paul E. Smith, Stefan H. Bossmann and Viktor Chikan, MspA Porin-Gold Nanoparticle Assemblies: Enhanced Binding through a Controlled Cysteine Mutation. Nano Letts., 8: 1229-1236, 2008
Veronica Pierce, Myungshim Kang, Mahalaxmi Aburi, Samantha Weerasinghe and Paul E. Smith, Recent applications of Kirkwood-Buff theory to biological systems. Cell Biochem. Biophys. 50:1-22, 2008
Myungshim Kang and Paul E. Smith, A Kirkwood-Buff derived force field for amides. J. Comput. Chem., 27:1477-1485, 2006.
Paul E. Smith, Chemical potential derivatives and preferential interaction parameters in biological systems from Kirkwood-Buff theory.
Biophysical J., 91:849-856, 2006