Protein-surface interactions in multimodal chromatography: a molecular modeling based investigation
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Authors
Banerjee, Suvrajit
Issue Date
2016-12
Type
Electronic thesis
Thesis
Thesis
Language
ENG
Keywords
Chemical and biological engineering
Alternative Title
Abstract
Next, a computational method was developed by combining short MD simulations and continuum solvent based coarse-grained free energy calculations to predict free energies of binding of the same protein faces studied through rigorous umbrella sampling simulations. The binding free energies from this method over predicted free energies from umbrella sampling. However, through suitable optimization of simulation time and coarse-graining parameters, the relationship between free energies from both methods were seen to be fairly linearly correlated. This new method was computationally much more efficient than umbrella sampling and was employed to calculate coarse-grained binding free energies of 101 faces each of proteins αChymotrypsinogen-A and Horse Cytochrome C on two different cation-exchange MM SAMs, Capto MMC and Nuvia cPrime, over a range of NaCl salt concentrations. Then, an iterative method was developed to calculate overall free energy of protein-MM surface binding and correlate these binding free energies to retention factors from isocratic chromatography. Subsequently, this correlation, combined with analytical expressions from the literature, was employed to correctly predict gradient elution salt concentrations for two other proteins, Ubiquitin and Ribonuclease-A, on Capto MMC and Nuvia cPrime and showed opposite selectivity trends in these two systems. Thus, a framework was established that could be used to predict selectivity in MM chromatography.
Description
December 2016
School of Engineering
School of Engineering
Full Citation
Publisher
Rensselaer Polytechnic Institute, Troy, NY