Paper BI-WeA5
Calculation of Adsorption Free Energy for Peptide-Surface Interactions using Molecular Dynamics Simulation Methods

Wednesday, October 22, 2008, 3:00 pm, 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. These methods, however, must first be developed and validated for this specific application. One of the most important areas for development is the assessment and validation of force field parameters that will enable the competition between amino acid residues of a peptide or protein and molecules of the solvent (i.e, water and salt ions) for the functional groups presented by a surface. One of the fundamental driving forces that control these types of interactions is the free energy of adsorption. We have therefore developed a method of accurately calculating the adsorption free energy of peptide-surface interactions using molecular dynamics simulations with an advanced sampling algorithm called biased replica-exchange molecular dynamics (biased-REMD). 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. A host-guest peptide model is used for these simulations in the form of TGTG-X-GTGT, where the T (threonine) and G (glycine) flanking sequences are the host residues and X represents a variable guest residue. Alkanethiol self-assembled monolayers (SAMs) with a broad range of polymer-like functionalities are being used as the adsorbent surfaces. The results of these simulations are being compared with complementary experimental studies using these same peptide-SAM systems in order to evaluate the accuracy of the force field, and to provide a basis for force field parameter modification for the development of a validated force field parameter set for the accurate representation of peptide-surface interactions. Once developed, these methods will be able to be applied to accurately simulate protein-surface interactions, thus providing a valuable resource to investigate protein-surface interactions at the molecular level.