(659f) Predicting Protein Stability At Biotic/Abiotic Interfaces With a Coarse Grain Model

Protein stability and activity at a biotic/abiotic surfaces are key factors for reliable performance of bio-chip based techniques such as biosensors. However, a detailed structural understanding of the protein-surface interaction is limited when experimental techniques are employed due to their limitations of atomic resolution. All-atom simulations are capable of providing atomistic information of protein structure on surfaces, however, the enormously large time scale required to generate thermodynamic quantities comparable to experimental results significantly restricts its application in such systems. In this work, we develop a carefully parameterized coarse grain model to compare protein structure generated from fast simulations with protein stability information from Sum Frequency Generation (SFG) spectroscopy and protein activity tests. A maleimide functionalized Self-Assembled Monolayer surface (SAMs) is used in experiments, which is simulated as a moderately-hydrophilic surface. Two proteins beta-gal and NsfB are tethered with different tethering sites in either loop or helix regions with different orientations on the surface. Simulation using the same set-up parameters generated protein structures that are consistent with the experimental results of protein stability and activity. Further studies from both simulation and experiment on a the alpha-helical peptide cecropin P1 is also performed with tethering at either the N- or C-termini . The results are also consistent between simulation and experiment. tour findings suggest that one may predict the structure and stability of mutant sequences of the peptide to inform further experiments on these systems and nicely augment the existing experiments.