Paper BI-TuM3
Molecular Dynamics Simulation of the Adsorption Behavior of Peptides with Secondary Structure to Functionalized Surfaces

Tuesday, October 21, 2008, 8:40 am, Room 202

While it is well understood that protein-surface interactions are of fundamental importance for understanding cell-surface interactions, very little is understood at this time regarding the molecular level events that control protein adsorption behavior. Molecular dynamics simulations methods have enormous potential for development as a tool to help understand and predict protein adsorption behavior. We are conducting molecular dynamics simulations to simulate the adsorption behavior of peptides with secondary structure to functionalized alkanethiol self-assembled monolayer (SAM) surfaces. Two types of structured peptides are being studied: (1) an alpha-helix forming peptide with a primary sequence of Ac-L-K-K-L-L-K-L-L-K-K-L-L-K-L-NH2 (LKalpha14), where L is leucine (nonpolar amino acid), K is lysine (positively charged amino acid), and Ac represents an acetylated end-group, and (2) a beta-sheet forming peptide, Ac–L-K-L-K-L-K-L-K-L–NH2 (LKbeta9). Two types of SAM surfaces are represented, (1) a CH3-SAM (hydrophobic surface) and (2) a COOH-SAM surface (negatively charged surface). Simulations are performed with the CHARMM force field and simulation package using explicitly represented solvent (150 mM Na+/Cl- in TIP3P water) with periodic boundary conditions. An advanced sampling method, known as replica-exchange molecular dynamics (REMD), is being applied in our simulations to generate Boltzmann-weight ensembles of states for each peptide-SAM system, with the resulting ensembles providing equilibrated structures of peptide behavior, both in bulk solution, and when adsorbed to each type of SAM surface. The resulting ensembles are then analyzed to provide a theoretical understanding of how the surface influences the secondary structure of both the LKalpha14 peptide and a pair of LKbeta9 peptides. In addition, assessment is also being made to quantitatively assess how each SAM surface and the peptide-surface interactions influence the water structure at the interphase region of the system relative to bulk water conditions. Simulation results are being compared with NMR, SFG, ToF-SIMS, and SPR experimental studies that are being conducted in a collaborative effort with Profs. Castner, Gamble, Stayton, and Drobny at the University of Washington.