Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

Legacy Department


Committee Chair/Advisor

Latour, Robert A

Committee Member

Stuart , Steven J

Committee Member

Bruce , David A

Committee Member

Vertegel , Alexey A


Protein adsorption to solid material surfaces is a complex phenomenon and various factors play a role in controlling these processes. Inherent limitations to understand these biological interactions using experimental approaches alone have led to the possibility of exploring these systems using computational molecular simulation methodologies. Before confidence can be placed on these computational protocols, however, rigorous validation of the applicability of these methods to accurately represent protein adsorption processes is needed. In this research, we evaluated the use of all-atom empirical force field (FF) based simulations using the CHARMM simulation program and FF for the study of peptide adsorption processes to a broad range of functionalized alkanethiol self-assembled monolayer (SAM) surfaces. Substantial deviations in adsorption free energy compared to experimental results were observed for hydrophobic and positively charged surface chemistries. These deviations were attributed to the combination of the under-prediction of the strength of non-polar peptide-surface interactions and the over-prediction of the strength of surface hydration under these interfacial conditions.
In order to address the identified problems in peptide adsorption behavior, the CHARMM program was extensively modified to incorporate the use of a dual FF in a single simulation to control interfacial and non-interfacial interactions independently. Parameterization of an interfacial FF was performed to correct the imbalance found in predicting the free energy of peptide adsorption based on comparisons with experimentally measured values, thereby creating an interfacial force field that more accurately represents protein-surface interactions.
Simulations performed using the Dual FF program enabled the molecular conditions that occur in an adsorption process to be more accurately represented compared to a simulation that uses a single FF parameter set to control the entire simulation. The developed Dual FF program can now be used to complement experimental studies for the investigation of protein-surface interactions, which should be useful for designing surfaces to proactively control protein adsorption behavior.



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