Bottlenecks protein structures

Genetic variants that do not affect protein structure, function, or synthesis could have attained polymorphic frequency by chance propagation (genetic drift) aided by a genetic bottleneck in which the population size was reduced. 

Moult J. A decade of CASP Progress, bottlenecks and prognosis in protein structure prediction. Curr Opin Struct Biol 2005 15 285-9. 

Formation of IBs during protein expression poses a bottleneck in the efficient downstream processing of therapeutic proteins. The reasons for IB formation are not fully known. Because translation is a slower process than protein folding, it is likely that the misfolding of translation intermediates plays some role. Further, since post-translational modifications, such as glycosylation and lyposylation, which are known to affect the secondary structure of proteins, are absent in bacteria, the non-modified protein structure may cause misfolding. The recovery of soluble... 

A major bottleneck in solving protein structures by NMR is the highly peakpicking and assignment of chemical shifts and NOEs. The strategy of the assignment process and stmcture calculation can be found in an excellent review [30]. In general, for a -labeled protein, a series of double/triple resonance experiments are... 

Protein expression and purification have traditionally been time-consuming, case-specific endeavors, and are considered to be the greatest bottlenecks in most proteomics pipelines (1) Escherichia coli (E. coli) is the most convenient and cost-effective host, although optimal conditions for the expression of different proteins vary widely. Proteins vary in their structural stability, solubility, and toxicity in this environment, resulting in differing rates of protein degradation,... 

Liquids and proteins are complex systems for which the smdy of dynamical systems has wide applicability. In the conference, relaxation in liquids (s-entropy by Douglas at the National Institute of Standards and Technology, nonlinear optics by Saito, and energy bottlenecks by Shudo and Saito), energy redistribution in proteins (Leitner and Straub et al.), structural changes in proteins (Kidera at Yokohama City University), and a new formulation of the Nose-Hoover chain (Ezra at Cornell University) were discussed. Kidera s talk discussed time series analyses in molecular dynamics, and it is closely related to the problem of data mining. In the second part of the volume, we collect the contributions by Leitner and by Straub s group, and the one by Shudo and Saito in the third part. 

Directed evolution bypasses the bottleneck of rational design and mimics natural evolution in a test tube to evolve proteins without knowledge of their structures. What fundamentally differentiates directed evolution from natural evolution is its power to significantly accelerate the process of evolution. As shown in Fig. 1, directed evolution uses various methods to generate a collection of random protein variants, called a library, at the DNA level. Followed by screening/selection of the library, protein variants with improvement in desired phenotypes are obtained. Usually, the occurrence of these functionally improved protein variants is a rare event thus, this two-step procedure has to be iterated several rounds until the goal is achieved or no further improvement is possible. 

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