284399 Adsorption of Helices and Coils On Negatively Charged Surfaces
Protein adsorption is a complex phenomenon partially because of the variety of amino acids present in a protein. The interaction between the protein and the surface is the result of the individual contributions of patches or segments found on the protein surface. The properties of these patches are defined by the individual amino acids that constitute them. There is a growing interest in adsorption studies using short peptide instead of the whole molecule because one can mimic the behavior of those patches. By using tailored peptides consisting of domains with specific structure and functionality, much is to be gained in the understanding the adsorption mechanism. We have experimentally explored the adsorption of a variety of diblock peptides on different substrates in the past. In this paper we present Monte Carlo simulations of the adsorption of one of such peptides onto negatively charged surfaces with the objective of elucidating the adsorption mechanism.
Monte Carlo simulations were performed to study the adsorption of a positively charged diblock peptide, consisting of five residues each of lysine (Lys) and alanine (Ala), onto negatively charged surfaces in the presence and absence of water. Initial conformations of helix and random coil were used. The procedure developed by Mungikar and Forciniti (Biomacromolecules, 7:239 (2006)) was adopted to perform the MC simulations. The peptide was placed at the center of the simulation box allowed to move towards a surface.
RasMol was used in this work to get a snapshot of the whole system at the end of the simulation and to determine the peptide’s secondary structure (helices, turns and random coils) after adsorption. These structures were confirmed/rejected by generating Ramachandran plots, which help monitoring the extent to which the peptide reorganizes at the surface. These plots were constructed using the torsion angles (Ф, Ψ) of the peptide generated during the production run of the simulation. In addition to mapping the conformational space sampled by the peptide at the surface, these plots were used to corroborate that RasMol definitions of structures (such as helix, turn and random coil) were reasonable. The Peptide End-to-End Distance was defined as the distance separating the N atom of the N-terminal Ala1 residue and the Cα of the C-terminus Lys10. A change in this value is an indication of a significant reorganization of the peptide’s global structure. Monitoring of changes in intra-molecular and peptide-solvent hydrogen bonding network of the peptide allows studying the structural rearrangement of the peptide at the surface. RasMol was used to study the changes in the intra-molecular hydrogen-bonding network of the peptide. Hydrogen bonding involving water was determined using the pair correlation functions between selected peptide atoms and water.
For both helix and random coil orientations, in water as well as vacuum, the Lys block rests near the surface whereas its Ala block is relatively away from the surface. Electrostatic force is a driving force for the adsorption of the peptide at the solid surface. In water, the helical peptide adsorbed in a side-on orientation whereas the random coil peptide had its Ala block extended into the bulk. This apparent ‘repulsion’ for the surface is actually due to the effect of solvent and is not seen in vacuum. The high-density water patch at the surface is probably the main reason. Transients in the adsorption process were observed. The peptide reaches the solid surface almost instantaneously and the slowly relax to reach a stable, and more compact, conformation.