(577f) Invited: Probing Surface Effects On the Orientation and Conformation of Adsorbed Proteins With Multiscale Simulations

Adsorption of biomolecules plays an important role in far range processes from biocatalysis to surface fouling.  Understanding and controlling adsorption remains elusive due to persistent difficulties in quantitatively coupling relevant thermodynamic and kinetic driving forces to the atomic scale features of these systems.  In principle, molecular dynamics or Monte Carlo simulations could be used to provide some of these insights.  However, the time and length scales accessible by classical simulations are normally insufficient.  This talk highlights recent examples from our group in the development and application of new methods to study protein adsorption, orientation and conformation on engineered and natural surfaces.  Three examples are presented.  The methods are explained and developed using an experimentally characterized model system (LK peptides adsorbing to self-assembled monolayers).  Following this the role of hydrophobicity and surface charge is explored on by studying the folding of a small helical peptide as a function of its distance from the surface.  The final example studies the role of the surface in controlling the structure and orientation of the protein statherin.  Throughout the talk we also focus on methods by which the biased (non-equilibrium) metadynamics simulations can be reweighed to recover unbiased estimates of experiment-relevant observables.