(699h) Modeling Protein Folding/Aggregation on Nanoparticle‐Based Biosensors in Complex Solvent Environments By a Coarse‐Grained Simulation System

Understand protein behavior in a complex environment is the key in rationalizing the design of many novel techniques such as protein biosensors based on novel nanoparticle (NP) materials. Protein folding and aggregation properties can be largely affected by the environments such as solid abiotic interfaces and complex co-solvents, which would directly affect the expected functionality or performance of the biosensors. Difficulties remain in applying current experimental methods to obtain a detailed picture of protein structures on a solid surface, so our ability is limited by these factors in the design of biosensor surface chemistry a priori for desired protein behavior. To address this point, in this work we present a coarse-grained simulation system that is able to model protein folding, misfolding, and aggregation on various NP surfaces and in the presence of co-solvents based on the Karanicolas and Brooks (KB) Go-like protein model. A flat-surface potential was first included and carefully parameterized based on a large experimental data set. This surface model has been shown in many studies to be able to reproduce and predict protein behavior at different types of surfaces as verified by experimental tests. Further effort in developing the surface potential was applied in describing surface curvature effects on protein behavior as a means of understanding nano-sized biosensor materials. Tanford's transfer free energy model was recently added to this simulation system as a descriptor of co-solvent effects. The energy of each part of the underlying folding/surface/solvation potential has been well balanced so that each element works collaboratively as a single complex environment for the protein. Together, this coarse-grained modeling system is expected to accurately predict the protein adsorption, folding/unfolding, aggregation, and protein-protein interactions in a complex environment as it would experience in differing cellular or solvent environments as well as in the context of a NP-based biosensor.