Improved Molecular Dynamic Simulation of Protein Devices: PEGylated Proteins and Protein Microarrays

Protein-based devices have great potential to change how we harness the power of biology. PEGylated proteins and protein microarrays are two such devices. PEGylation covalently bonds polyethelyene glycol (PEG) chains onto a protein’s primary structure to increase a protein’s stability in the body. Protein microarrays covalently tether proteins onto a solid surface and has transformative applications for detection assays. However, for both devices, functionalization often renders it inactive.

We have developed a coarse-grain molecular simulation model that has been shown to accurately predict optimal functionalization sites. This presentation explains this model and reports its use on a the commercially-relevent protein β-lactamase. The in silco screen reveals the best candidate sites for PEG and surface attachment. Experiments then validate these results.

The results for both protein devices are presented and indicate that device attachment site strongly affects thermostability and that configurations more stable than wild type are possible. Moreover, by using the same protein for both devices, we show that optimal site locations for one device is not predictive for the other. Finally, PEGylation simulation indicate stabilizing PEG/protein structures contradict current theory