protein folding and assembly

Literature Review

The first question to ask is how fast do proteins fold? other proteins that are dennatured

fold to the original structures in microseconds, showing that a foldinng mechanism exists.

There is a challenge in the prediction of protein structures through use of atomic physical

model (Zhang, 2008) . The most reliable proof of a folding mechanism is if it fastens the

prediction of protein structure in physical models (Shell et. al., 2008).. The local

structuring of folding and assembly mechanism takes place first at different sites within

the chain, and the structures either assemble or fold with the other structures. The folding

and assembly process is applied in predicting protein original structure use of AMBER96

force with a surface area solvent model (Zhou, 2011) . Moreover, sampling is done by

molecular dynamics replica change. Starting with denatured conformations, the fold and

assembly method converges to 2.2A from the old structure of protein that is tested. In

conclusion, the fold and assembly process is a sure method of knowing how proteins fold

physically.

Protein folding has two problems, computational and physical (Dill et. al, 2008).. . the

physical problems is about how fast proteins fold. In test tube experiments of protein

refolding, the protein molecules start in a disnatured state that has no order. and fold

when original conditions restores. In addition, folding is stochastic meaning that the

native structure of a protein is reached through various trajectories from various

denatured confromations (Ozkhan et. al, 2007). Folding also takes place fast, at times in
microseconds to reach native conformation order. Even the most simple disorder to order

change, like sodium chloride crystalization takes time. The conformational search is not

random.

The second challenge is computational that involves prediction of the native structure of

proteins from its sequence of amino acids. Success in this field may lead to progress in

drug discovery that is computer based. There is an increasing success in the prediction of

protein structures. The prediction of most structures of protein makes use of

conformational preferences that is databased. Nevertheless, for reasons that follow, it

would be appropriate to get a high resolution prediction of protein structure in models

which are physics based (Kmiecik et.al, 2007). First, it would place the protein structure

understanding as well as driving forces on deep and physical foundation. for instance,

such methods can elucidate the protein folding physical route. Secondly, it will allow non

native prediction.

There has been a viewpoint that solution to the physical folding up of proteins can assist

in solving the problem of predicting protein structure. If there was enough insight of the

folding of proteins, can it be applied in protein structure speed up prediction algorithms.

in history, insights into process of folding come fromfoldng kinetics studies. the folding

is hierarchal and secondary structures are formed before tertiary structures. nevertheless,

folding routes derived from experiments are insufficient to providing a folding principle

needed in informing search algorithms. the folding route is an event sequence description,

basically secondary structure formation, observed for a protein under specific condition.

in contrary,a folding principle involves a quantitative model starting from any chain

conformation and predict quick routes to the original state.

for success to be realized in prediction of protein structure that is physics based, two

questions must be solved, one being is the force field effecive and is there sufficient

conformational sampling. there are problems with force fields of molecular mechanics.

AMBER94 overstabilize helices and AMBERS96 favors structures that are extended

(Thompson et. al, 2010). nevertheless, there are successes, showing that force fields are

better. the major bottleneck to prediction of protein structure is that the conformational

methods (Kim et. al, 2009). a folding principle is the most predictive and useful if it the

folding routes that can speed up the predictions original protein structure prediction. it is

questioned if the protein structure is achievable in a model in many tiny protein. a search

strategy that is mechanism based is used which is believed to be a strategy used by

proteins to fold. folding and assembly samples a small part of the conformational part

that would be sampled by traditional methods . it is this search strategy that eables usto

effectively sample conformational space's relevant parts.

according to folding and assembly mechaism,on the start of folding conditions, an

unfolding chain explores local structures at various independent point along the chain. the

local structures low energy cnformational basins, stabilized by hydrophobic contacts and

always contain small turn and helical structures. apart from being stable indepedently, the

loal structures can recruit adjuscent amino acids within the chain sequence to create

additional contacts, folding or assembling (Joo et. al, 2014). in the two cases, the chain

get ordered inreasingly. the folding and assembly is backed up by latice model that shows

that the search strategy can find optimal states of large sequences and by master equation

studies shows consistency with experiments that have been carried out.
conclusion

we have explored the protein folding and assembly that is a hypothesis on the routes

through which proteins fold and a conformational serch based mechanism method for the

prediction of proteins native structure from the sequences of amino acids. there is an

extensive evidence that is up to date that force with physics based methods can attain a

high resolution presently found in the best methods of bioinformatics, atleast for tiny

proteins. it has not been investigated in the lind tests like the prediction event of structure

in the CASP protein,andit is believed that challenges of the force field is a problem in a

few cases, like in the src-SH3 domain.

the folding and assembling model explains how protein folding is so effective, in spite of

the differences and micoscopic trjectories diversity i protein structures. it theorizes that

proteins apply a trategy of divide and rule. tiny local peptides parts of the chain gives

conformational preferences, on which other structures assemble and grow. the logic is

that earliest folding time scales are short for chain explortaion of aspects that are more

non-local of the conformational space,and hence the folding early stage is a minimal

conformational entropy loss process in each step. the local structures with metastability

that is sufficient on fast time-scales asseemble and grow thus increasing structure

amounts on time scales that are longer.

as no experiment is currently available to capture enough microscopic detail to get the

possiblities of various microscopic trajectories, its utility is the reliable evidence for such

a mechanism. the folding and assembling conformational sampling is faster compared to

other methods (Mehdi et. al, 2013).

references

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Problem. Annual Review of Biophysics, 37, 289–316.

http://doi.org/10.1146/annurev.biophys.37.092707.153558

Joo, H., & Tsai, J. (2014). An Amino Acid Code for β-sheet Packing Structure. Proteins,

82(9), 2128–2140. http://doi.org/10.1002/prot.24569

Kim, D. E., Blum, B., Bradley, P., & Baker, D. (2009). Sampling bottlenecks in de novo

protein structure prediction. Journal of Molecular Biology, 393(1), 249–260.

http://doi.org/10.1016/j.jmb.2009.07.063

Kmiecik, S., Gront, D., & Kolinski, A. (2007). Towards the high-resolution protein

structure prediction. Fast refinement of reduced models with all-atom force field. BMC

Structural Biology, 7, 43. http://doi.org/10.1186/1472-6807-7-43

Mehdi M., Xin G., Jianhua Z. H. (2013). ; Assessing protein conformational sampling

methods based on bivariate lag-distributions of backbone angles, Briefings in

Bioinformatics, Volume 14, Issue 6, Pages 724–736, https://doi.org/10.1093/bib/bbs052

Ozkan, S. B., Wu, G. A., Chodera, J. D., & Dill, K. A. (2007). Protein folding by zipping

and assembly. Proceedings of the National Academy of Sciences of the United States of

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Mechanical Potentials for Helical Peptides and Proteins. PLoS ONE, 5(4), e10056.

http://doi.org/10.1371/journal.pone.0010056

Zhang, Y. (2008). Progress and challenges in protein structure prediction. Current

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