Project

Our project modeled the interaction between a glucose molecule and a previously engineered and tested glucose biosensor (Fig. 1).

Figure 1 - Our biosensor in its environment. The protein, colored yellow and in the drawing method New Cartoon, is in an aqueous environment, which is shown by the blue molecules. Glucose is bound to the biosensor, and is colored red.

We modeled the biosensor in the presence and absence of its target, glucose (Fig. 2, 3). The biosensor we researched contains a periplasmic binding proteins and protein fluorophores. These proteins and other proteins are made up of long chains containing a specific sequence of amino acids. There are 21 core amino acids within the human body, each containing a carboxyl group, amino group, and an R-group all bonded to a central carbon atom. The R-groups are what determine the identity of the amino acid, and it is made up of different atoms.

Atoms are the smallest unit of matter from which most of the world, including our biosensor, is built. Three properties largely contribute to the behavior of atoms: charge, sterics, and free energy. In a neutral atom, the number of positively-charged protons and negatively-charged electrons are equal, resulting in a zero net-charge. However, the removal or addition of electrons throws this balance off, creating a positively or negatively charged atom. Similar to magnets, positive atoms and negative atoms will attract each other, while atoms of the same charge repel. Sterics involves the spatial arrangement of atoms. When atoms get too close to each other, their electron clouds repel each other, creating an unstable molecule. Finally, Gibbs free energy measures the ability to do work. Atoms try to move towards a lower energy potential, and lower their ability to do work. All three of these factors affect the behavior of atoms, and therefore the properties of proteins.

Figure 2 -Our biosensor without a glucose molecule. The biosensor is colored yellow (representation: NewCartoon).

Figure 3 - Our biosensor bound to a glucose molecule. The biosensor is colored yellow (representation: NewCartoon) and the glucose molecule is colored blue and red (representation: VDW).

Our biosensor requires the presence of glucose to induce a change in the periplasmic binding protein (Fig. 4, 5). This change in shape allows the protein fluorophore to illuminate and provide a visual indication of the presence of glucose. The proteins are illuminated using FRET, or fluorescence resonance energy transfer. FRET allows one protein to transfer energy so another protein, which then fluoresces. This procedure is dependent on distance, therefore the change in shape is necessary to bring proteins close enough together to allow for illumination.

Figure 4 - This is the catalytic domain of our original biosensor without glucose bound to it.

Figure 5 - This is the catalytic domain of our original biosensor with glucose.