Cysteine is commonly used to attach peptides onto gold surfaces. In this work, we show that the inclusion of an additional linker of four residues in length (-PPPPC) of a rigid, hydrophobic nature, is a better choice for forming peptide self-assembled monolayers (SAMs) with well-ordered structure and high surface density. We compare the structure and function of the nonfouling peptide EKEKEKE-PPPPC-Am with EKEKEKE-C-Am. Circular dichroism (CD), attenuated total internal reflection Fourier transform infrared spectroscopy (ATR-FTIR), and molecular dynamics (MD) results show that EKEKEKE-PPPPC-Am forms a secondary structure while EKEKEKE-C-Am has a random structure. Surface plasmon resonance (SPR) sensor results show that protein adsorption on EKEKEKE-PPPPC-Am/gold is very low with small variation while protein adsorption on EKEKEKE-C-Am/gold is high with large variation. X-ray photoelectron spectroscopy (XPS) results show that both peptides have strong gold-thiol binding onto a gold surface, indicating that their difference in protein adsorption is due to their assembled structures. Further experimental and simulation studies were performed to show that -PPPPC is a better linker than -PC, -PPC, and -PPPC. Finally, we extend EKEKEKE-PPPPC-Am with the cell-binding sequence RGD and demonstrate control over specific vs. non-specific cell adhesion without using poly (ethylene) glycol (PEG). Adding a functional peptide to the nonfouling EK sequence avoids complex chemistries that are used for its connection to synthetic materials.

In this work, we report a study on the differential hydration of carboxybetaine and sulfobetaine using molecular simulations. The coordination number, spatial distribution, dipole orientation distribution, and residence time of water molecules around the positively charged group (N(CH(3))(3)(+)) and negatively charged group (COO(-) for carboxybetaine and SO(3)(-) for sulfobetaine) were investigated to compare the hydration of these two betaines. The results show that the negatively charged group of sulfobetaine has more water molecules around it than that of carboxybetaine, while the water molecules around the negatively charged group of the carboxybetaine have a sharper spatial distribution, more preferential dipole orientation, and longer residence time. The behavior of water molecules around the positively charged group of sulfobetaine is similar to those around the positively charged group of carboxybetaine. For both sulfobetaine and carboxybetaine, the positively charged groups are surrounded by more water molecules than the negatively charged groups, whereas the water molecules around the negatively charged groups are more ordered than those around the positively charged ones. We also investigated the hydration free energy of these two molecules with the free energy perturbation method and found that their values are all considerably lower than that of oligo(ethylene glycol).

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A primary goal in molecular simulations is to modify the potential energy of a system so that properties of the simulation match experimental data. This is traditionally done through iterative cycles of simulation and reparameterization. An alternative approach is to bias the potential energy so that the system matches experimental data. This can be done while minimally changing the underlying free energy of the molecular simulation. Current minimal biasing methods require replicas, which can lead to unphysical dynamics and introduces new complexity: the choice of replica number and their properties. Here, we describe a new method, called experiment directed simulation that does not require replicas, converges rapidly, can match many data simultaneously, and minimally modifies the potential. The experiment directed simulation method is demonstrated on model systems and a three-component electrolyte simulation. The theory used to derive the method also provides insight into how changing a molecular force-field impacts the expected value of observables in simulation.