Modeling an Enzyme Active Site using Molecular Visualization Freeware.

Biomolecular visualization skills are paramount to understanding key concepts in the biological sciences, such as structure-function relationships and molecular interactions. Various programs allow a learner to manipulate 3D structures, and biomolecular modeling promotes active learning, builds computational skills, and bridges the gap between two dimensional textbook images and the three dimensions of life. A critical skill in this area is to model a protein active site, displaying parts of the macromolecule that can interact with a small molecule, or ligand, in a way that shows binding interactions. In this protocol, we describe this process using four freely available macromolecular modeling programs: iCn3D, Jmol/JSmol, PyMOL, and UCSF ChimeraX. This guide is intended for students seeking to learn the basics of a specific program, as well as instructors incorporating biomolecular modeling into their curriculum. The protocol enables the user to model an active site using a specific visualization program, or to sample several of the free programs available. The model chosen for this protocol is human glucokinase, an isoform of the enzyme hexokinase, which catalyzes the first step of glycolysis. The enzyme is bound to one of its substrates, as well as a non-reactive substrate analog, which allows the user to analyze interactions in the catalytic complex.

Meeting report: BioMolViz workshops for developing assessments of biomolecular visual literacy.

While molecular visualization has been recognized as a threshold concept in biology education, the explicit assessment of students' visual literacy skills is rare. To facilitate the evaluation of this fundamental ability, a series of NSF-IUSE-sponsored workshops brought together a community of faculty engaged in creating instruments to assess students' biomolecular visualization skills. These efforts expanded our earlier work in which we created a rubric describing overarching themes, learning goals, and learning objectives that address student progress toward biomolecular visual literacy. Here, the BioMolViz Steering Committee (BioMolViz.org) documents the results of those workshops and uses social network analysis to examine the growth of a community of practice. We also share many of the lessons we learned as our workshops evolved, as they may be instructive to other members of the scientific community as they organize workshops of their own.

Approach toward the total synthesis of 5-hydroxyaloin A.

The synthesis of a thiomethyl analogue of 5-hydroxyaloin A has been achieved using benzyne and naphthyne [4 + 2] cycloadditions with substituted furans. A regiocontrolled cycloaddition was achieved using a silicon tether, and a regioselective ring opening was accomplished using a sulfide as a directing group.

Deconstructing cytisine: The syntheses of (+/-)-cyfusine and (+/-)-cyclopropylcyfusine, fused ring analogs of cytisine.

A novel fused tricyclic analog (11) of cytisine has been prepared (coined 'cyfusine') and determined to have high affinity at neuronal nicotinic acetylcholine receptors. A [3+2] cycloaddition protocol permitted entry into a 3,4-differentially difunctionalized dihydropyrrole (7). The penultimate cyclization was accomplished using the modified Van Tamelen conditions developed in our earlier synthesis of (+/-)-cytisine. Sequential ring-forming reactions ([3+2] cycloaddition/cyclopropanation/pyridone cyclization) gives a unique cyclopropyl analog (16) possessing a skeleton isoatomic with that of cytisine.