H2020Индивидуална стипендия2016–2018

MEMBRANEPROT · Membrane proteins – development of new computational approaches and its application to G-Protein Coupled Receptors

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-03-01 → 2018-02-28
Финансиране от ЕС: 177 599 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Компютърни модели и алгоритми за машинно обучение анализират взаимодействията между мембранните протеини, като например връзките между GPCR рецепторите и G-протеините. Това помага за по-доброто разбиране на функционалните механизми и структурните свойства на протеините в клетките.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Membrane proteins – development of new computational approaches and its application to G-Protein Coupled Receptors

The identification of protein complexes and interactions is key for the understanding of cellular organization and machinery. Due to the challenges of obtaining sufficient experimental data about those interactions, computational tools and methodologies are emerging as reliable alternatives. It is especially true that machine-learning algorithms hold an astonishing potential for studying protein interactions by enabling the identification of biologically relevant patterns, which accelerates our knowledge of the functional mechanism of proteins within cells. My Marie Sklodowska-Curie Individual Fellowship have been focused on the development and application of computer modelling techniques that went beyond the current state-of-the-art, leading to quantitative and reliable molecular-level predictions of hot-spots at protein-protein complexes, protein-protein interfaces and membrane protein interface. These new predictors and tools were applied to the understanding of the physicochemical, structural and dynamic properties of GPCR/G-proteins and GPCR/Arrestin complexes. The results illuminated essential mechanisms of GPCR selectivity from a new perspective including dynamic mechanisms and yielded novel methods and approaches to serve in the study of membrane protein systems and their functional mechanisms.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Protein-protein tridimensional (3D) structures are fundamental for structural biology and drug discovery. Many docking algorithms were developed for that purpose, but they have limited accuracy in generating native-like structures and identifying the most correct one, particularly in the case of membrane proteins such as G-protein Coupled Receptors (GPCRs). In order to deal with these complex systems and overcome the limitations of existing software, we will develop and optimize computational approaches and construct novel combinations of mature methodologies, to serve in the study of membrane proteins in general. In particularly, we will focus in: i) improving the search and scoring algorithms for the docking process of membrane proteins, ii) developing software to accurately predict the high-order oligomers interfacial residues, and iii) constructing a docking algorithm able to predict their 3D oligomeric structure. Our new approaches will be applied to a relevant biological system: the dopamine receptor type 2 (D2R), a typical member of Class A GPCRs involved in many cognitive, emotional and motor functions. D2R acts by ligand-dependent signalling through two major systems: the G-proteins, and the Arrestin proteins (Arr-s). How ligands determine the preference for one or the other is not yet understood at the molecular level, and this precludes both the characterization of pathway selectivity and the design of biased ligands. More importantly, the physiological relevance of oligomerization for this process is still topic of vigorous debate. Therefore, building on both my unique expertise and Prof. Bonvin well-known impact in methodological development, this project will yield novel methods and approaches to serve in the study of membrane protein systems and their functional mechanisms, benefiting the entire research field. It will also provide truly new fundamental knowledge and insights into the selectivity of D2R signalling.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITEIT UTRECHT · UtrechtКоординаторНидерландия