Victor Bloomfield, Principal Investigator

Preferential Solvation: A Method for Obtaining Cosolvent and Water
Concentrations at a Macromolecular Surface

  Mixed solvent systems are important in the understanding of the structures and stabilities of macromolecules. For example, urea and guanidine HCI 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 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.

  PS data are available for many cosolvents with many proteins; the Bloomfield lab gathered further data on cosolvents with DNA. Unfortunately, interpreting PS data is not straightforward. Current theories are limited in their practicality and have yet to be tested against known solvent distributions. Despite the wealth of PS data, no one had yet used these data to determine where cosolvents lie. The goals of this project were to develop a practical method for obtaining the cosolvent/ water composition at a macromolecular surface from PS measurements and to test existing theories. Simulations are ideal for this purpose because it is difficult to obtain the solvent distributions from purely experimental methods.

  The first step toward understanding PS was to determine the excluded-volume contribution. When cosolvents and waters are differently sized, it is well known that the surface cosolvent: water distribution is not like that of the bulk solvent. What portion of preferential solvation is due to size differences alone as opposed to interactions? To answer this question, these researchers followed their earlier work by running grand-canonical Monte Carlo simulations (using cell lists) of binary mixtures of two-dimensional hard circular disks up against a hard wall. They then studied mixtures of three-dimensional hard spheres. The researchers tested existing preferential solvation theories by simulating many size rations and compositions to mimic experimental systems. These simulations are cpu-intensive because of (i) large size ratios and (ii) low concentrations of the large disks/spheres.

  After determining the excluded-volume part of preferential solvation, the researchers added short-ranged interactions-van der Waals and hydrogen-bonding interactions-and, later, long-ranged interactions such as electrostatics to understand how each of these interactions contribute to PS.