The latest BiophysJ cover image is based on the article “Molecular Interactions of Alzheimer’s Biomarker FDDNP with Aβ Peptide,” written by Christopher Lockhart and Dmitri K. Klimov. Klimov explains the scientific purpose of the image, as well as the work that went into it, in the blog post below:
The cover art represents the molecules of FDDNP biomarker bound to Abeta peptide implicated in Alzheimer’s disease. The structure is one of countless conformations generated by replica exchange molecular dynamics simulations in explicit solvent. Because of exhaustive sampling in our simulations, we believe that they correctly represent the actual binding mechanism. We found that FDDNP binds to Abeta peptide at two binding sites located near the central hydrophobic cluster and in the C-terminal by mostly utilizing hydrophobic interactions. Importantly, the FDDNP ligands are self-aggregated and tend to bind to Abeta peptide as clusters, which penetrate into Abeta core.
It is commonly assumed that FDDNP biomarker labels Alzheimer’s Abeta fibrils in brain tissues during positron emission tomography (PET) scans. However, FDDNP interactions with Abeta monomers and oligomers, which are also present in the brains of Alzheimer’s patients, have never been probed. Consequently, our study of FDDNP was motivated to fill this gap by providing the molecular level information about FDDNP binding to Abeta monomer and potentially helping to improve the quality of PET data.
The image was rendered using the Chimera program, developed at the University of California, San Francisco. Care was taken in how the ligands and peptide were represented with the goal of providing the best clarity. We chose to separate the different molecular species by model and color. We modeled the peptide backbone as a ribbon while using the ball-and-stick model for peptide side chains and modeled the ligand using the stick model. We colored the two peptide binding sites in light and dark green and left the rest of the peptide in light gray. The ligands were colored in orange to distinguish them from the peptide. The structure was oriented so the two binding sites and the ligands bound to those sites were clearly visible. Water was removed from the structure for clarity.
The authors are very grateful to the Biophysical Journal for selecting this image to be displayed on the cover. We believe that scientific figures must not solely be attractive for aesthetic purposes but must also be clear to concisely convey the information to readers.
– Dmitri K. Klimov