Date of Award


Document Type


Degree Name

Doctor of Philosophy (PhD)

Legacy Department



Latour, Robert A

Committee Member

Stuart , Steven J

Committee Member

Bruce , David A

Committee Member

Vertegel , Alexey


The process of protein adsorption to material surfaces is highly complex and it is one of the most fundamental concepts upon which progress in the field of bioengineering is based. The strategic design of material surfaces for optimal utility in specific biological environments is absolutely dependent upon a thorough understanding of the mechanisms underlying protein adsorption, yet there is still a very limited understanding of these mechanisms. The primary reason for this lack of understanding is that protein adsorption is a dynamic process which occurs at the atomic and macromolecular scale, where experimental analyses provide a view that is static and too coarse to elucidate the stepwise processes behind this critical biochemical phenomenon. In recent years, continual improvements in speed and efficiency of computational hardware and simulation techniques have enabled the use of molecular simulation for studying systems of the size necessary for examining the mechanistic details of protein adsorption (tens to hundreds of thousands of atoms). Of the various forms of molecular simulation, all-atom empirical force field molecular dynamics (MD) simulation has shown the greatest potential for exploring the nature of protein adsorption because it offers a dynamic view of nanosecond-scale processes with atomistic detail. However, a shortcoming of the application of MD in studying protein adsorption is that the most widely used MD force fields (i.e., equations and parameter sets used for calculating structural and energetic properties) have been designed and validated for simulations of solvated molecular systems in the absence of solid surfaces. To address this shortcoming of an otherwise extremely powerful research tool, an initial evaluation of the applicability of existing MD force fields to model systems of structured peptides interacting with functionalized material surfaces is warranted. The work presented here encompasses that initial evaluation of force fields. Numerous detailed analyses of water, ions, and peptides were completed in order to provide the most accurate and comprehensive examination of simulated peptide adsorption available. As a result of this work, simulation methods for these unique systems were tested and determined to be appropriate for accurately representing experimental results. Also, a comparative evaluation of force field performance identified the force field that most consistently reflects experimental findings.