LYSINE ACETYLATION · Molecular mechanisms of protein Acetylation Activation: A combined molecular simulation and molecular Biology Approach
6РП — Действия „Мария Кюри“
- Период
- 2005-09-01 → 2007-08-31
- Финансиране от ЕС
- 0 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Молекулярните механизми на ацетилирането на лизин се изследват чрез компютърни симулации и биологични опити, като например при протеините на HIV-1. Разбирането на тези процеси помага за създаването на модели, които могат да служат за разработване на нови лекарства срещу СИДС.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Цел на проекта
Nature uses acetylation of lysine residues to modulate the affinity of a variety of nucleic acid binding proteins for their target DNA or RNA. Important examples of such acetylation-based signalling activation processes include the acetylation of Lys residues in histones and the activation of HIV-1 integrase for enhancing the binding affinity to DNA. Surprisingly, no systematic study aimed at understanding the basic molecular mechanisms of acetylation has been performed so far. Here we propose a combined computational chemistry and molecular biology approach, which will uncover several aspects of the Lys acetylation process. The proponent will carry out the computations at the International School for Advanced Studies within a close collaboration with the Molecular Medicine Lab of the International Centre for Genetic Engineering and Biotechnology directed by Mauro Giacca.Specifically:(i) I will provide the description of the molecular mechanism of tGcn5 enzyme-catalysed Lys acetylation process using hybrid Car-Parrinello QM/MM method;(ii) I will characterize the structural rearrangements associated to acetylation in tGcn5-histone complex will be carried out using classical molecular dynamics simulations;(iii) I will construct a structural model for DNA-acetylated protein HIV-1 integrase. Each computational study will be accompanied by experimental mutagenesis data, which will be used to validate my results.Results of this highly interdisciplinary work will provide a description of fundamental aspects of Lys acetylation-based signalling as well as provide a structural model of the DNA-HIV-1 integrase complex, which in turn can be used as a template for designing potential anti-AIDS drugs.
Оригинален текст от CORDIS (на английски).
Участници
- INTERNATIONAL SCHOOL OF ADVANCED STUDIESКоординаторНиво градИталия
Връзки
Данни: CORDIS, © Европейски съюз