Perspectives on blended learning through the on-line platform, LabLessons, for Chemistry

The effectiveness of blended learning was evaluated through the integration of an online chemistry platform, LabLessons. Two modules, Formation of Hydrogen and Titration, were designed by college mentors alongside classroom chemistry teachers to engage and allow high school students to better comprehend these scientific topics. The pre-lab modules introduced the students to experiments they were expected to perform in class the following day. The modules consisted of an introduction as well as either a visualization and/or simulation specific to each topic. Students and teachers who utilized LabLessons were surveyed to establish a preliminary research on the use of technology in classrooms. Student and teacher surveys demonstrated LabLessons to be an interactive and helpful tool to improve students' understanding of conceptual ideasPeer Reviewe

Hydration dynamics at fluorinated protein surfaces

Water-protein interactions dictate many processes crucial to protein function including folding, dynamics, interactions with other biomolecules, and enzymatic catalysis. Here we examine the effect of surface fluorination on water-protein interactions. Modification of designed coiled-coil proteins by incorporation of 5,5,5-trifluoroleucine or (4S)-2-amino-4-methylhexanoic acid enables systematic examination of the effects of side-chain volume and fluorination on solvation dynamics. Using ultrafast fluorescence spectroscopy, we find that fluorinated side chains exert electrostatic drag on neighboring water molecules, slowing water motion at the protein surface

Fluorine: A new element in protein design

Fluorocarbons are quintessentially man‐made molecules, fluorine being all but absent from biology. Perfluorinated molecules exhibit novel physicochemical properties that include extreme chemical inertness, thermal stability, and an unusual propensity for phase segregation. The question we and others have sought to answer is to what extent can these properties be engineered into proteins? Here, we review recent studies in which proteins have been designed that incorporate highly fluorinated analogs of hydrophobic amino acids with the aim of creating proteins with novel chemical and biological properties. Fluorination seems to be a general and effective strategy to enhance the stability of proteins, both soluble and membrane bound, against chemical and thermal denaturation, although retaining structure and biological activity. Most studies have focused on small proteins that can be produced by peptide synthesis as synthesis of large proteins containing specifically fluorinated residues remains challenging. However, the development of various biosynthetic methods for introducing noncanonical amino acids into proteins promises to expand the utility of fluorinated amino acids in protein design.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90596/1/2030_ftp.pd

Rational Design of Protein Stability: Effect of (2S,4R)-4-Fluoroproline on the Stability and Folding Pathway of Ubiquitin

BACKGROUND: Many strategies have been employed to increase the conformational stability of proteins. The use of 4-substituted proline analogs capable to induce pre-organization in target proteins is an attractive tool to deliver an additional conformational stability without perturbing the overall protein structure. Both, peptides and proteins containing 4-fluorinated proline derivatives can be stabilized by forcing the pyrrolidine ring in its favored puckering conformation. The fluorinated pyrrolidine rings of proline can preferably stabilize either a C(γ)-exo or a C(γ)-endo ring pucker in dependence of proline chirality (4R/4S) in a complex protein structure. To examine whether this rational strategy can be generally used for protein stabilization, we have chosen human ubiquitin as a model protein which contains three proline residues displaying C(γ)-exo puckering. METHODOLOGY/PRINCIPAL FINDINGS: While (2S,4R)-4-fluoroproline ((4R)-FPro) containing ubiquitinin can be expressed in related auxotrophic Escherichia coli strain, all attempts to incorporate (2S,4S)-4-fluoroproline ((4S)-FPro) failed. Our results indicate that (4R)-FPro is favoring the C(γ)-exo conformation present in the wild type structure and stabilizes the protein structure due to a pre-organization effect. This was confirmed by thermal and guanidinium chloride-induced denaturation profile analyses, where we observed an increase in stability of -4.71 kJ·mol(-1) in the case of (4R)-FPro containing ubiquitin ((4R)-FPro-ub) compared to wild type ubiquitin (wt-ub). Expectedly, activity assays revealed that (4R)-FPro-ub retained the full biological activity compared to wt-ub. CONCLUSIONS/SIGNIFICANCE: The results fully confirm the general applicability of incorporating fluoroproline derivatives for improving protein stability. In general, a rational design strategy that enforces the natural occurring proline puckering conformation can be used to stabilize the desired target protein