Relevant projects
pMHC-HNMMC
“Exploring peptide/MHC dissociation landscapes using Hierarchical Natural Move Monte Carlo” (BIO2017-83650- P)
[Bernhard Knapp, PI, 2018-2019; Jordi Villà-Freixa, PI, 2019-2021]
Binding between peptides and major histocompatibility complexes (MHCs) is one of the most important processes in the human immune system. If the MHC repertoire of a human cannot stably bind a specific peptide then no effective immune response against this antigen can be elicited. Therefore understanding peptide/MHC interaction has broad implications for drug discovery in cancer, allergies, and autoimmune diseases.
A large number of sequence- and training-based peptide/MHC binding prediction methods are available. However, these tools answer the question if a peptide binds an MHC and not why. Molecular Dynamics (MD) simulations based methods go one step ahead and allow for insights into the structural behaviour of peptides in the MHC binding groove but to date no MD simulation could show how peptides detach from MHCs. This is possibly due to too high computational resource consumption of MD simulations.
Here we proposed that a combination of advanced sampling algorithms would allow insights into peptide/MHC detachment processes at a structural level and in reasonable runtime. In particular we used combinations of coarse-graining, hierarchical natural Move Monte Carlo, and local/global temperature changes. Thereby we obtained insights into general detachment patterns of peptides from over different MHC alleles. Based on long simulations we looked for detailed characterisation of the peptide/MHC structural dissociation landscapes. Being able to structurally characterise peptide dissociation from MHCs on a large scale has profound implications for drug discovery in a large number of human health conditions.
EU-FP7 325146. SOCIAL ECOSYSTEM FOR ANTI-AGING, CAPACITATION AND WELLBEING. SEACW (2013-2015)
The objective of the project is to create an ecosystem including tools for the provision of training, literacy, information and awareness in the area of ICT for active and healthy aging. There are two main target groups: agents for social inclusion, and the elderly and the general population. For the first target group, agents of social inclusion, the platform intends to be an online meeting point and a means to improve their training skills. For the second target group, the elderly and the general public, the platform will include both training material and practical tools to implement the knowledge acquired. The tools will be designed specifically for the elderly (interfaces, SmartTV, etc.), will enable participants to immediately apply the knowledge and at the same time will encourage them to keep on learning. The platform will combine different tried and tested technologies, but will be unique and innovator as a whole. The pilot will be implemented in 15 regions, covering 15.000 participants. In addition to the platform, the project will conduct two studies, one on the state of the art and the other on the impact of ICT for active and healthy ageing.
Marató TV3: “Modulation of immune receptors function as a novel therapeutic strategy for acute CNS damage” (2012-2015)
The existence of different types of immune receptors with the capability to regulate microglia/macrophage function opens a new window for the development of new neuroprotective strategies in acute CNS damage. This project aims to analyse the therapeutic potential of some of those proteins (CD200R, TREM-2 and the CD300 family of receptors) in different experimental in vitro and in vivo models. This proposal will be developed by 5 teams covering a wide range of expertise including bioinformatics, molecular immunology, neurobiology, neuropathology, and behavioural neuroscience. The role of the CBBL is to provide support on protein structure and protein interaction predictions.
aScidea (2011-2013)
The promotion of aScidea Computational Biology Solutions, SL, (twitter: @ascidea) became an important activity in the lab for some years. Currently, the company is lead by former lab members, although the CBBL members formally discontinued their collaboration with the company in 2013.
ActivA (2009-2011)
The interest in participating in the development of tools with real biomedical impact led us to join efforts with the O2HLink company, in an AVANZA project funded by the Spanish Ministry of Industry, on the development of an integrated portal for 3D visualization of biological data, ActivaCentral. You can see some videos here.
The project ActivA purpose was to enhance and expand rehabilitation programs and facilities for a network of patients with Cystic Fibrosis, to create a network of interaction between research organizations, medical institutions and communities of patients, and to establish a more proactive communication stream based on the interchange of information to optimize the results of the factors involved. This was aimed at generating a true therapeutic community. The project focussed on the development of a WebGL based portal that provided an easy to use interface for clinicians, researchers and patients all related to a common disease, cystic fibrosis. In addition to the technological aspects of the project, lead by O2HLink, Inc., our lab was involved in the scientific developments. On the one side, we worked on developing a 3D model for the CFTR chloride channel, which is the key protein which deficiencies (lack of expression or malfuncioning) produced by a high number of different mutations, cause the disease. The model has been recently submitted for publication. In addition, the project served the CBBL to enter the world of web services workflow development with Taverna, and we provided some pipelines devoted to structural prediction or even molecular dynamics of target proteins that should be accessible through the portal. Although the overall result of the project lied behind the expectations, it paved the way for the use and development of new technologies within the CBBL, from advanced statistics through R to workflow deployments, as well as opened the possibility to continue with studies on the CFTR and membrane proteins.
VPH NoE (2008-2013)
The Virtual Physiological Human Network of Excellence (VPH NoE) has been designed with ‘service to the community’ of VPH researchers as its primary purpose. The aims of the network range from the development of a VPH ToolKit and associated infrastructural resources, integration of models and data across the various relevant levels of physiological structure and functional organisation, through to VPH community building, training activities and support.
EU-FP6. QosCosGrid (2006-2009)
An FP6 STREP project, in which the lab contributed two home-developed software tools (Adun and ByoDyn) as use cases of the development and implementation of a new paradigm for quasi-opportunistic simulation of complex systems applications. The project evolved into a foundation that is currently active and engaged in other projects.
Complex systems are defined as systems with many interdependent parts which give rise to non-linear and emergent properties determining the high-level functioning and behavior of such systems. Due to the interdependence of their constituent elements and other characteristics of complex systems, it is difficult to predict system behavior based on the ‘sum of their parts’ alone. Examples of complex systems include bee hives, bees themselves, human economies and societies, nervous systems, molecular interactions, cells and living things, ecosystems, as well as modern energy or telecommunication infrastructures. Arguably one of the most striking properties of complex systems is that conventional experimental and engineering approaches are inadequate to capture and predict the behavior of such systems.
To complement the conventional experimental and engineering approaches, computer-based simulations of complex natural phenomena and complex man-made artifacts are increasingly employed across a wide range of sectors. Typically, such simulations require computing environments which meet very high specifications in terms of processing units, primary and secondary storage, and communication. Supercomputers constitute the de factotechnology to deliver the required specifications. Acquiring, operating and maintaining supercomputers involve considerable costs, which many organizations cannot afford. The working assumption of the QosCosGrid project is that a grid could be enhanced by suitable middleware to provide features and performance characteristics that resemble those of a supercomputer. We refer to such a grid as quasi-opportunistic supercomputer. The QosCosGrid projects aim is to develop such a system.
EU-FP6. BioBridge (2006-2009)
Through this FP6 STREP project, we engaged in the study of diagnostic and eventually prognosis on COPD patients using an integrated knowledge management to clinical data through simulation environment, which led us to get interested in the developing of integrative tools for translational medicine.
The omics revolution of recent years has led to an explosion of data. This information, however, is currently fragmented, which limits progress on the understanding of the underlying mechanisms of complex chronic disorders. A major constraint for small and medium enterprises (SMEs) in the biomedical field is the lack of appropriate tools for data integration and simultaneous analysis of different levels of information. BioBridge proposes to tackle this problem with the creation of the BioBridge portal, where 1) structured databases including genomic, proteomic, and metabolomic information for the metabolic pathways affected by these disorders will be 2) integrated to model the underlying metabolic networks. This, in turn, will be utilised by 3) a simulation environment for simultaneous analysis of multilevel data able to improve existing knowledge on complex disorders.