How vibrational energy exchange study in proteins can shed the light on important biological functions
| العنوان: | How vibrational energy exchange study in proteins can shed the light on important biological functions |
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| المؤلفون: | Maggi, Luca |
| المساهمون: | Carloni, Paolo, Stamm, Benjamin |
| المصدر: | Aachen : RWTH Aachen University 1 Online-Ressource (80 Seiten) : Illustrationen, Diagramme (2020). doi:10.18154/RWTH-2020-09171 = Dissertation, RWTH Aachen University, 2020 |
| بيانات النشر: | RWTH Aachen University, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | allosteric modulation, vibrational energy exchange, protein dynamics, molecular dynamics, ddc:530 |
| الوصف: | Dissertation, RWTH Aachen University, 2020; Aachen : RWTH Aachen University 1 Online-Ressource (80 Seiten) : Illustrationen, Diagramme (2021). = Dissertation, RWTH Aachen University, 2020 Proteins retain specific structures and dynamics that are directly connected with their biological functions. In many cases, these functions are intimately linked to the vibrational energy exchange, within protein structure. Experimental, theoretical and computational studies associated vibrational energy exchange to biologically relevant events such as allosteric modulation, conformational rearrangement and heat dissipation subsequent to a chemical reaction. Therefore, a deeper understanding of vibrational energy exchange is instrumental to gain a better comprehension of significant macromolecule functions. The intrinsically complex topology and the broad range of different chemical interactions make vibrational energy exchange a hard problem to tackle and thus it is still an elusive phenomenon, which can even present counter intuitive features. Recent experimental findings, for instance, showed vibrational energy exchange occurs mostly through non-bonded residue contacts instead of through stronger backbone covalent bonds and is faster in residues with a larger solvent exposed surface. In order to better elucidate how vibrational energy exchange takes place in proteins and to draw a more complete description, this work presents a theoretical picture able to give a reasonable, albeit qualitative, explanation to these experimental results. Our description relates vibrational energy exchange with topological features, that in turn are directly associated to dynamical properties. This theory is supported by in-silico experiments, i.e. Molecular Dynamics Simulations, carried out on a pharmacological relevant transmembrane receptor, Muscarinic Acetylcholine Receptor M2 which belongs to the large family of G-Protein Coupled Receptors. Furthermore, using our new theory and previous computational findings we have built a Markov Chain-based model in order to describe the allosteric modulation for the M2 receptor as communication process occurring via vibrational energy exchange among proteins residues. This model is useful for identifying relevant residues of the protein that take part in this communication. This information can ultimately be instrumental for developing new allosteric drugs, which can, present higher selectivity and less side-effects Published by RWTH Aachen University, Aachen |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75bd1a6f94bddc46916936808014ad33Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....75bd1a6f94bddc46916936808014ad33 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |