(139a) Simulations of Adsorption Properties for Charged Polypeptides on Hydrophobic Chromatography Surfaces

           There
is a pressing need for computational design tools to accelerate the development
of bioprocess purifications.  Our project seeks to fill this need by developing
computational methods for predicting adsorption of peptides and proteins on
hydrophobic chromatography surfaces. In this work, our previous mesoscopic
method (1,2) for successfully obtaining low-coverage adsorption thermodynamics
for protected peptides in hydrophobic chromatography, based on a Langevin
lattice of dipoles and ions (ALLD), has been extended to systems with charged
biochemical solutes.  Modifications include appropriate positioning of
counterions in the neighborhood of acidic and basic amino acids in pH=7 and
pH=2 via geometric and annealing algorithms, as well as obtaining the
electrostatic contributions of fully-charged solutes and ions.  Parameter
determination and successful predictions have been based on new experimental
data taken in a strategic manner to minimize the number of molecular variables
changed with conditions, substances and surfaces (3).

The presentation
will describe our extended Langevin dipole methodology, some atomistic
simulations of peptides and aprotinin in an aqueous environment with added salt
that were used in decisions to set up the mesoscopic systems, and comparisons
of the final results with available data.

Also to be
discussed are effects of conditions on preferential orientations, as well as
sensitivity of final results to changes in model assumptions such as lattice
dimensions, dipole size, and orientational averaging.

References

1. K. Makrodimitris, E.
   Fernandez, T. Woolf, J. O'Connell, Analytical Chemistry  77, 1243
   (2005).
2. K. Makrodimitris, E.
   Fernandez, T. Woolf, J. O'Connell, Molecular Simulation, in press
   (2005).
3. A. Freed, J. O'Connell, E.
   Fernandez, to be submitted to J. Chem. Eng. Data (2005).

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