Mixed solvent systems are important in the understanding of the structures and stabilities of macromolecules. For example, urea and guanidine HCl have long been used to study protein denaturation; alcohols are condensing agents for DNA. To understand cosolvent-macromolecular interactions, it is necessary to determine where cosolvents are-do they tend to lie within the bulk solvent or do they prefer to associate with the macromolecule? The preferential solvation (PS) measurement, a straightforward (although tedious) experiment which can be done in many laboratories, is a potential method for obtaining the water/cosolvent composition near a macromolecular surface. PS measures the amount of cosolvent and water in the environs of the macromolecule. Currently, there is PS data on many cosolvents with many proteins; the Bloomfield lab has also gathered data on cosolvents with DNA. Unfortunately, interpreting PS data is not as straightforward as performing the experiment. Current theories are limited in their practicality and have yet to be tested against known solvent distributions. Despite the wealth of PS data, nobody has determined where cosolvents lie.
Karen E.S. Tang, Research Associate
This project is developing a practical method for obtaining the cosolvent/water composition at a macromolecular surface from PS measurements and testing existing theories. Simulations are ideal for this purpose because simultaneous PS and solvent distributions are known. It is difficult to obtain solvent distributions from purely experimental methods. The first step in understanding PS is to determine the excluded-volume contribution. When cosolvents and waters are differently sized, it's well known that the surface cosolvent/water distribution is not like that of the bulk solvent. What portion of PS is due to size differences alone as opposed to interactions? To answer this question, grand-canonical Monte Carlo simulations (using cell lists) of binary mixtures of two-dimensional hard circular disks up against a hard wall are being run. A move onto mixtures of three-dimensional hard spheres is then done. Many size ratios and compositions are simulated to mimic experimental systems and to test existing PS theories. These simulations are computationally intensive because of large size ratios and low concentrations of the large disks/spheres. Hence, the Supercomputing Institute's Basic Sciences Computing Laboratory is used. After determining the excluded-volume part of PS, short-ranged interactions (van der Waals and hydrogen-bonding interactions) are added, and later, long-ranged interactions such as electrostatics are added to understand how each of these interactions contribute to PS.
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URL: http://www.msi.umn.edu/about/publications/annualreport/ar2000/depts/Biochem_MolBio_BioPhys/bloomfield.html |
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