Question

In: Chemistry

Look at situation where there are 2 molecules of the same protein, which means same primary...

Look at situation where there are 2 molecules of the same protein, which means same primary sequence. In addition they fold at the same time in the same funnel. Each protein, which is represented by a marble, is predicted to take a special path as it moves down the funnel during the folding process. While it folds, it is possible that the two proteins collide on the way down the funnel, and as a result of this collision, one or both of those proteins misfolds (forms a kinetic trap). As with any collision, energy is exchanged between the colliding molecules, and we can assume that the energy changes as a result of the collision contribute to potential misfolding. How can one represent how energy changes (thermodynamic state functions) in the funnel model as collision has to take place for both proteins to account for the resulting misfolds?

Solutions

Expert Solution

At the top of the funnel the protein exists in a number of random states that have relatively high entropy and high enthalpy. Progress down the funnel is given by collapse and reconfiguration. The reconfiguration occurs as a motion through adjacent, thus geometrically similar, conformations, by a Brownian-like motion. The acquisition of native structure reduces the free energy and drives the protein towards the bottom of the funnel, while enthalpy is progressively reduced. The driving force is working against entropy, which decreases simultaneously with entropy. The progress of folding can be described by the parameter Qi , the fraction of native contacts in the state i:

Qi = C(i) / C(n)

where C(n) is the number of contacts formed by residue pairs in the native state and C(i) is the number of such contacts conserved in state i. The molten globule state is rather compact but still highly non-native. The transition state is located at a higher value of Qi , thus closer to the native structure. If Q does not increase uniformly, but in few large steps, then the protein folding occurs through nucleation. After passing through the transition state, there is a single low energy state corresponding to the native conformation. This drives the protein to fold completely, while the absence of other relevant minima prevents from misfolding

The folding funnel hypothesis is a specific version of the energy landscape theory of protein folding, which assumes that aprotein's native state corresponds to its free energy minimum under the solution conditions usually encountered in cells. Although energy landscapes may be "rough", with many non-native local minima in which partially folded proteins can become trapped, the folding funnel hypothesis assumes that the native state is a deep free energy minimum with steep walls, corresponding to a single well-defined tertiary structure.

[ Source : Wikipedia. ]


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