Proteins are the active players in the cells and carry out most of the significant functions throughout biology such as metabolism, immunity, and maintaining structural integrity. Protein characteristic behaviors such as dynamics and residue level co-evolution play a critical role in determining the detailed behaviors of any given protein. We have employed a range of computational methods: molecular dynamics simulations, principal component analysis of conformations, molecular modeling, and co-evolution analysis of sequences to attempt to understand the molecular mechanisms in membrane transporters and transmembrane proteins.
The systems considered here include the Multi-Drug-Resistant efflux pumps present in
gram-negative bacteria and the classical cadherins observed in epithelial cells. We gain critical insights into mechanisms from these studies regarding functional dynamics and identifying structural features that play key roles in the efflux of cyclic lipids in HpnN transporters.
Further, our studies newly identify a novel cis interface between classical cadherin. This originates from a strong correlation between co-evolving residues, suggesting that this interaction plays an important role in cell-cell adhesion. Based on this work, we have been able to devise a workflow incorporating these methods that provide new insights for selection of sites to target to inhibit function
