The Noid lab collaborates with experimental groups at Penn State to address interesting biochemical questions as well as active matter research questions. These collaborations allow us to approach important problems and provide theoretical insight into experimental results.
An active collaboration is with the Cremer group, investigating the effects of small molecules on interfacial properties of polymers. Another avenue where we are contributing theory and simulation results is in the form of a collaborative project on active matter with the Sen group. Previously, we have collaborated with the Showalter lab to investigate the biophysical properties of intrinsically disordered proteins and have also performed simulations to elucidate the effects of glycosylation upon protein folding.
Older Projects
1. Intrinsically disordered proteins
In recent years it has become increasingly clear that a large class of proteins perform essential biological functions, despite lacking a well-defined equilibrium structure in isolation. These proteins are frequently involved in signal transduction processes and often undergo a striking disorder-order transition upon binding to an appropriate partner. Although many studies have proposed various functional advantages for intrinsic disorder, many questions remain regarding their basic biophysical properties and the biological significance of these properties. In close collaboration with the Showalter lab at Penn State, we have been examining the interaction of the disordered C-terminal tail of the FCP1 protein (in blue below) and its interaction with the Rap74 domain of Transcription Factor IIF (in red ). While our simulation studies have provided some mechanistic insight into the disorder-order transition for this particular IDP, our collaboration has also suggested a critical role for hydrophobic forces (see ITC data at right) and frustrated interactions in IDP function.
2. Impact of glycosylation
A large class of proteins are covalently modified by the attachment of a complex carbohydrate to the amide group of Asn sidechains. This modification not only impacts the protein function and cellular localization, but also impacts the dynamics and thermodynamic stability of the protein. Moreover, since this bulky glycan is introduced co-translationally, i.e., before the protein folds, it is reasonable to expect that the N-linked glycan may substantially impact protein folding. Nevertheless, the impact of N-linked glycosylation upon protein biophysics remains largely unexplored. Our studies suggested that the biophysical effects of glycosylation are not simply due to steric interactions, but reflect specific attractive interactions, such as hydrogen bonding and hydrophobic interactions, between the peptide and glycan. Moreover, our simulations suggest that these effects are very sensitive to the sidechain adjacent to the glycosylation site. Finally, we have demonstrated that the biophysical effects of glycosylation upon short peptides are surprisingly consistent with their effects upon full-size glycoproteins.
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