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An Efficient Protein Structure Prediction Using Genetic Algorithm
Published in Abdel-Badeeh M. Salem, Innovative Smart Healthcare and Bio-Medical Systems, 2020
Mohamad Yousef, Tamer Abdelkader, Khaled El-Bahnasy
Levinthal’s paradox [1] states that there is no way for a protein structure to try and fold into all of its possible conformations to form its native structure because it will take a massively long time, but in fact proteins take only a few seconds or less to reach their native fold. This implies that every protein follows a folding pathway. In addition, Anfinsen’s thermodynamic hypothesis [2] states that, for small globular proteins, the native structure is determined by the protein’s amino acid sequence. This also infers that, at normal conditions (temperature and medium concentration, etc.), when folding process ends, the native structure is stable and has the lowest free energy. Levinthal’s paradox and Anfinsen’s hypothesis are the foundations of ab initio PSP.
Hydrogen deuterium exchange mass spectrometry applied to chaperones and chaperone-assisted protein folding
Published in Expert Review of Proteomics, 2019
Florian Georgescauld, Thomas E. Wales, John R. Engen
Protein folding – the physical process through which a protein acquires its native conformation – has long been studied and continues to be one of the biggest scientific challenges in structural biology. From the birth of the protein folding field, theoretical and experimental studies have shown that the folding phenomenon is not based on random searching for the native state (the Levinthal paradox), but rather involves appearance of partially structured entities called folding intermediates [10]. While the major classical methods (e.g., enzymology, spectroscopy methods such as fluorescence, etc.) reveal that folding is happening, detailed information about exactly how structure is obtained or how it changes during the process is difficult to obtain. The HDX MS approach appears ideal for characterizing folding intermediates and folding pathways. During folding, a protein experiences its two most extreme conformations: the fully unfolded state which has all its amides protons accessible to solvent for exchange, and the final folded form which has the fewest accessible amide protons. These two states, fully unfolded and completely native, can easily be distinguished with HDX MS and unlike other more traditional methods, HDX MS provides both location and kinetic information during the transition between the two states (e.g., [3–5,11],). Simultaneously, populations concomitantly present in solution can be observed, and changes within those populations selectively monitored [12]. In more simple terms, HDX MS can assist in determined what is doing what, when, and how fast.