UTF-8Modeling hydrophobic effectBGSU CHEM 4450/5450 General Biochemistry I Final Project
Caitlyn Menicucci
Over the past two weeks you've explored properties that affect miscibility of two liquids and considered the difference between properties that affect individual particles vs. those that arise from collections of particles. The Final Project of this semester for our evening sessions is focused on investigating what gives rise to the tendency for soluble proteins to fold with their hydrophobic amino acids on the interior and 'hidden' from the aqueous solvent. You can work towards a better understanding of this phenomenon by modifying the following model to recapitulate a similar behavior ('understanding' in this case means knowing what is required to cause the behavior).
Below, there are two compartments with the following characteristics:
- each has a polymer of 24 linked, green particles (all of the same particle type, 'Pl'). Note: any change you make to the particles of one polymer will by definition affect the other polymer too!
- each polymer is 'pinned' to the center of the compartments (small white 'x' symbol)
- the radius of gyration (Rg) for each polymer is plotted on the graph at the right as a measure of how compact or folded each polymer is. Rg is a calculated value that essentially measures the average distance between all monomers in a polymer. Extended polymers have larger Rg values, whereas folded polymers have smaller Rg values.
The Challenge: Make changes to the compartments (adding solvent particles, changing particle properties, etc.) to control how folded the polymers are. Your goal will be to make the polymer in the left compartment as compact/folded as possible and the other as extended as possible. In other words, create conditions in the two compartments that maximize the difference between their radii of gyration.
Rules:
- the properties and composition of the polymers must remain identical (i.e. any change to one polymer must be made for the other as well).
- any other particles you choose to add must behave like liquids
Note:
- to select an individual particle in the polymer, hold down the <Shift> key and left-click with your mouse (double-left-click to modify the polymer particle properties).
- you are asked to output the radius of gyration data to Excel for questions below. To do this, click the "List data sets" button (leftmost button) above the graph and double click on one of the channels. Channel 0 corresponds to the left polymer, channel 1 to the right (see pink labels on polymers). Paste into MS Excel. There are three columns:
- column 1: 'i' (the index of the data point measured)
- column 2: the time point (i.e. measured in thousands of femtoseconds)
- column 3: the radius of gyration for the given polymer at that index/time point
Answer the following questions in the document below. Send me a screenshot of your responses by e-mail. Then collaborate with your group to write up a short report as instructed in the Google Document linked here: http://tinyurl.com/obvo2xo
1.) The goal of this exercise was to design solvent conditions that would cause two identical polymers to behave differently - one folded and the other as extended as possible. Describe in complete sentences what you did to solve the challenge (one folded and one extended polymer, ‘liquid’ solvent, hydrophobic polymers)? Be sure to describe whether your strategy worked and how what evidence you used to come to that conclusion.
To get my compound folded, I increased my protein:proteininteractions and I made sure the solvent:solvent forces were strong enough but not so strong that they invaded the polymer. I decreased the protein:solvent interactions (Pi-Ck). Based on last weeks discussion, I got the folded part of my protein to approx. RG less than or equal to 4.
For my unfolded protein, this was harder. I had to increase my protein:solvent interactions and make my protein:protein interactions slightly less while making sure the other protein stayed folded. This was determined accurate when I readed 6, again, based on last weeks standards of approx greater than or equal to an RG of 6. Mine approached 6 but I think that if I let it run longer, the solvent would have "invaded" the protein more, opening it up.
2.) Let your model run for enough time for the two polymers to achieve their different behaviors. Output the Rg vs. time data and plot it in Excel. Paste the overlaid plots of Rg vs. time to support your argument.
3.) According to your model, what is the most important factor controlling how folded/extended the polymers are?
I think the interactions between the solvent and polymer really indicate how well something will fold. It is also helpful to have good polymer:polymer interactions to fold and less to unfold. Overall, I think solvent:protein interactions caused the biggest change with my simulation.
4.) A similar phenomenon occurs in nature where proteins fold with hydrophobic surfaces sequestered on their interior away from aqueous solvent. Does your polymer exhibit similar behavior (i.e. is your polymer ‘hydrophobic’ and does your solvent have properties that resemble aqueous solvent?
My left side, the folded side, exhibits hydrophobic behaviour while the right side is starting to resemble hydrophiylic, especially since the solvent is "invading" the protein.
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