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Blobulation is an approach for edge-detection in protein sequences based on contiguous hydrophobicity, which we originally developed for a specific long intrinsically disordered protein (the prodomain of BDNF).
The blobulator is a webtool for blobulation, which allows the user to blobulate any sequence, and visualize the results while adjusting the two blobulation parameters to detect more edges for higher-resolution (“zooming-in”) or detect fewer edges for a more tractable visualization (“zooming-out”).
Collaborative work with the Cheng lab at Washington University-St Louis was just published in eLife! “Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites” used photolabeling and Mark’s coarse-grained MD simulations to identify two binding sites for polyunsaturated fatty acids (DHA), and functional studies with modifications to determine which site is responsible for the effects of DHA. This paper also provided another test of the method for lipid affinities from density distributions that we published here.
After a successful Fall 2022 rotation cycle, the lab has three new members! We are very excited to welcome Noureen Abdelrahman, Mariadelia Argüello Acuña, and Regina Salzer, who are all MS students in Computational and Integrative Biology.
Noureen completed her B.S. at Lafayette College, and will be working on a new collaboration with the Shain lab on adaptation of ATP synthase in thermophiles. Mariadelia completed her B.S. at Universidad de Costa Rica, and will be continuing Shriya’s project (with the Klein lab) on the role of sphingolipids in Caulobacter. Regina will be headquartered in the Griepenburg lab but will also collaborate with Jahmal on simulations of membrane-nanoparticle interactions. Welcome!
Jesse successfully defended his MS thesis “SARS-CoV-2 Envelope Protein Induces Membrane Curvature Through Asymmetric Hydrophobic Mismatch” in front of his committee, CCIB, and many enthusiastic family members today. We are thrilled that he will be continuing onto do his PhD in the Brannigan lab!
Shriya successfully defended her MS thesis “Using molecular dynamics simulations to elucidate a role for bacterial ceramide” in front of her home lab (the Klein group), her committee, CCIB, and many enthusiastic family members today. Shriya started working on this computational project when she couldn’t do experiments during the pandemic – and now she is planning to join a CCIB computational group for her PhD!
We were thrilled to hear that Group Alumni Shashank Chavali (MS 2016) just defended his PhD dissertation “Use of Lab-Evolved Proteins to Guide Development of Inhibitors that Target HIV-1 TAR RNA” at the University of Rochester. He will be moving on to a joint postdoc between the Sindelar and the De La Cruz labs at Yale University, studying motor proteins. Congratulations Dr. Chavali!
Liam’s paper “Spontaneous lipid binding to the nicotinic acetylcholine receptor in a native membrane” has been published! It is a contribution to the JCP Special Collection in Honor of Women in Chemical Physics and Physical Chemistry, and is also the culmination of Liam‘s doctoral research, so it is particularly special to me! This paper uses coarse-grained molecular dynamics and a metric for lipid binding affinities to provide quantitative ranking of specific lipid binding in a very complex membrane. It builds on his previous papers identifying specifically-bound lipids in model membranes.
Tom’s paper investigating binding of ketamine analogues to GPCRs was just published in ACS Chemical Neuroscience! “Ketamine Metabolite (2R,6R)-Hydroxynorketamine Interacts with μ and κ Opioid Receptors” used atomistic MD simulations, streamlined alchemical free energy perturbation calculations, and G-protein recruitment assays to show that a ketamine metabolite is an inverse agonist for two opioid receptors. These results may help explain the mechanism by which ketamine successfully treats treatment-resistant depression. The paper includes a new pharmacological model for binding of ligands with multiple protonation states.
Liam successfully defended his dissertation “Boundary lipids of nicotinic acetylcholine receptors in model and native membranes” in front of his committee, CCIB, and many enthusiastic family members today. He did a fantastic job. We wish him luck at his new postdoc in the lab of Dr. Edward Lyman at the University of Delaware. The lab won’t be the same without you, Liam!