Hi, I am going to prepare a proposal under the title of (An combined study of protein structure, function and dynamics with presentations to human health and the environment). So could you please give your view and an idea on the aim, objective, hypothesis, and the best method to complete this project. Thank you for any comment and support.
Hi Arsalan,
You should look at previous work published from Prof Eugene Shakhnovich's group at harvard university correlating organismal firness with protein fitness landscape to get an idea for the proposal you are exploring. He has demonstrated how protein fitness of dihydrofolate reductase, in terms of thermal stability and catalytic turnover of individual protein varints, lead to differing firness levels at the population level. Notable papers include, but are not limited to,:
Bershtein, S., Choi, J.-M., Bhattacharyya, S., Budnik, B. & Shakhnovich, E. Systems-Level Response to Point Mutations in a Core Metabolic Enzyme Modulates Genotype-Phenotype Relationship. Cell Reports 11, 4, 645-6 (2015).
Bershtein, S., Mu, W., Serohijos, A.W.R., Zhou, J. & Shakhnovich, E.I. Protein Quality Control Acts on Folding Intermediate to Shape the effects of Mutations on Organismal Fitness. Molecular Cell 49, 1, 133 - 144 (2013).
Serohijos, A.W.R., Rimas, Z. & Shakhnovich, E.I. Protein biophysics explains why highly abundant proteins evolve slowly. Cell Reports 2, 2, 249 - 256 (2012).
Bershtein, S., Mu, W. & Shakhnovich, E.I. Soluble oligomerization provides a beneficial fitness effect on destabilizing mutations. Proc. Natl. Acad. Sci. USA 109, 4857 - 4862 (2012).
Proteins are the most used macromolecule in the human body and its structure-function is greatly related to how it interacts with the human body. Simple misfolded proteins, called prions, are the cause of several diseases including Alzheimers. I suggest looking at studies with protein structure-function errors and its correlates to human health
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