Structural Biochemistry/Proteins/Protein Folding to New Enzymes
Enzymes go through several mechanisms in order for it to survive and thrive in the biological world. The fact that proteins can fold amongst itself in their functional states after the process of synthesis is one of the most fascinating mechanisms ever studied by researchers.
Basis of Protein Folding
In a living cell, protein folding occurs in a highly complex environment and uses different utility proteins for function. Some proteins' sole function is to protect the incomplete folding process from malfunctioning or the polypeptide chain from interactions other than folding. It is especially protective against factors that could lead to aggregation, folding catalysis or others that can slow down the process of protein folding in relation to isomerization or the forming of disulphide bonds. There are exceptions to the process of folding where auxiliary proteins are not needed to protect the sequence. Evidence shows that the code for protein folding is contained within the protein sequence. This is because studies have been shown where proteins undergo in vitro processes and can still function the same way as a protein supported by auxiliary proteins, as long as the in vitro occurs within conditional environments.
Protein Folding Mechanisms
There have been a mass amount of studies performed on the mechanism of protein folding recently. Many researchers have also been receiving plenty of successful feedback on these conducted experiments. Many different types of applications, such as experimental and theoretical, have provided the basis for the main reason of studying protein folding in the first place.
One of the strongest cases of protein folding into new enzymes is known as the "stochastic process". The stochastic process is a random process that calculates different possibilities of pathways and conclusions to the final result of the experiment. The stochastic process is opposite to the deterministic process, which is having one initial possible result occur after an experiment is conducted. The stochastic process may initially start off with one possible result, but might end up with several different, plausible results, some more probable than others, after the experiment is completed.
Biased parties, nonetheless, believe that the original interactions between proteins are still more reliable and stable than newly-tested interactions and techniques. Studies have shown that the sequences of proteins can still be found in pristine condition even if the sequences live in very complex environments within a cell. However, when a protein folds on itself incorrectly or does not maintain to stay folded in the living cells, diseases of different types can occur.
An example of a possible group of diseases is called amyloidosis. Some common diseases that are derived from amyloidosis are Alzheimer's Disease and spongiform encephalophaties. These diseases occur when the protein is aggregated from failure of folding. An interesting fact about amyloidoses is that the formation of the aggregates show similarities to the property of polypeptides and not just a feature of proteins that suffer from poor or inadequate protein folding. It is not normal to find such amyloid aggregates in biological evolution, which begs the question if there are a variety of mechanisms that have been tampered with over time. In order to prevent such diseases from developing and to stop such mechanisms from mutating into insufficient mechanisms, the study of the folding of proteins is crucial to understanding the structure of a protein as well as the function to all living cells.
Issues and Possible Results of New Protein Folding Mechanisms
Although groundbreaking discoveries have been mass produced in the protein folding community, several issues arise. Tampering with the folding of a protein can alter the initial theory as to why humans should manipulate a natural occurring mechanism. Because of the high volume of magnitude and conformational changes done on a protein sequence, it is more likely that the experiment could lead to the stochastic process in producing several pathways and results. Also, due to a strong presence of heterogeneity at the end of the folding process, the changing of the protein folding sequence can alter desired results. According to Christopher Dobson, a researcher at Oxford Centre for Molecular Sciences in the University of Oxford, "there are two main approaches to try and overcome this issue".
The first approach lies with the use of biophysical techniques that can monitor the properties of the amino acid sequence as the folding takes place. Because the process of folding occurs in a rapid fashion, several outlets of methods are needed to map out the individual properties of the sequence. For example, an ultraviolet circular dichroism can be used to monitor the secondary structure of evolution and fluoresence microscopy can monitor the progress of the tertiary structure.
The second approach is to use protein engineering to study the mechanism of protein folding. Protein engineering is a particularly good method of studying the folding process because it can also map out the transition states of the protein sequence. Examination of the folding and unfolding parts of the mechanism takes place upon mutation of the individual amino acids in the sequence. By studying the intermediate steps of the folding process, the mechanism shows that there is a formation of native-like proteins surrounding a number of important amino acids. This provides evidence that for another mechanism called "nucleation-condensation", where the majority part of the protein sequence rapidly forms once the nucleus of the entire process has been found.
Dobson, Christopher M. Biochem. Soc. Symp. (2001) 68, (1–26) (Printed in Great Britain). http://symposia.biochemistry.org/bssymp/068/bss0680001.htm. Last accessed: 1 Dec. 2011.