Final Report Summary - MACROMOLECULESATWORK (Unveiling the physics of cellular processes: new approaches to study macromolecules at work)
The Macromolecules At Work project aimed at combining different computational methods to study the Physics of specific cellular components and processes which involve biological macromolecules, especially concentrating on the study of polyelectrolye DNA chains and analogous biopolymers investigating on their interaction with cellular structures and on the mechanisms of modifications of their physical properties.
The most prominent scientific challenge was to include all the multiscale physical phenomena related to polyelectrolytes in solution into a consistent theoretical modeling approach. In addition, the computational aspect of the project was also non trivial, and supercomputing techniques and resources had to be employed to provide unique scientific insights. The project was granted hundreds of thousands CPU hours by the Barcelona Supercomputing Centre research panel.
In line with the philosophy of the project, we solved the problem of theoretical modeling by assembling a computational framework to address different cellular processes. Some of the software was already available (NAMD, Gromacs) and some was developed in house during the first half of the project. The different components of the framework were up and running after the first part of the project, providing an accurate and feasible tool to study biological processes at different scales, enabling the overall framework to
target macromolecular behaviour from femtoseconds to microseconds, from angstrom to micrometer.
We applied to different cellular processes important for bio- and nano-technology opening different research lines. These research lines were pursued in collaboration with different scientists to enhance dissemination and providing a cross-field perspective:
- With Dr. Miscione of Bologna University, Dr. Freixa and Prof. Muñoz of Barcelona Biomedical research park (PRBB) the triose phosphate isomerase protein (TPI) using MareNostrum resources. This has led to a very detailed study of the conformational stability of a key protein related to Alzheimer.
- With Dr. Monica Pickholz, we focused on the coarse grained simulation of the dynamics of encapsulation of local anesthetics into a liposome using the MARTINI forcefield. This study shed light on the assembly/adsorption mechanisms of small molecules to cellular membranes.
- At the highest scale, we concentrated on spherical colloids as the most effective way to date to model bio-polyelectrolytes in cells (DNA, proteins, ..). With Prof. Pagonabarraga, electrophoretic processes were studied with unprecedented detail with a Poisson-Boltzmann description coupled to lattice Boltzmann model to solve the hydrodynamics.
Research extending the capabilities of our computational framework was also pursued to enable code development on NVIDIA Graphics Processing Units. Apart from the scientific project impact, recognized by the publications produced and by the fact that at least three different groups are willing to collaborate and use the tools and knowledge created, its overall impact is foreseen to be relevant as it directly targets bio- and nano- technology (key research areas indicated by the EU) and has produced highly interdisciplinary results at the fundamental (electrophoresis, drug delivery) and technological (GPU computing) level. The scientist was invited to visit different research groups and also hosted researchers during the project. The broad echo of the project is demonstrated by the outstanding amount of multidisciplinar work that was executed, bringing together collaborators from different fields and by the fact that MacroMolecules At Work was chosen by EU to publish a comment for general readership in the Projects magazine, reaching out a wide audience well beyond scientific communities.
The most prominent scientific challenge was to include all the multiscale physical phenomena related to polyelectrolytes in solution into a consistent theoretical modeling approach. In addition, the computational aspect of the project was also non trivial, and supercomputing techniques and resources had to be employed to provide unique scientific insights. The project was granted hundreds of thousands CPU hours by the Barcelona Supercomputing Centre research panel.
In line with the philosophy of the project, we solved the problem of theoretical modeling by assembling a computational framework to address different cellular processes. Some of the software was already available (NAMD, Gromacs) and some was developed in house during the first half of the project. The different components of the framework were up and running after the first part of the project, providing an accurate and feasible tool to study biological processes at different scales, enabling the overall framework to
target macromolecular behaviour from femtoseconds to microseconds, from angstrom to micrometer.
We applied to different cellular processes important for bio- and nano-technology opening different research lines. These research lines were pursued in collaboration with different scientists to enhance dissemination and providing a cross-field perspective:
- With Dr. Miscione of Bologna University, Dr. Freixa and Prof. Muñoz of Barcelona Biomedical research park (PRBB) the triose phosphate isomerase protein (TPI) using MareNostrum resources. This has led to a very detailed study of the conformational stability of a key protein related to Alzheimer.
- With Dr. Monica Pickholz, we focused on the coarse grained simulation of the dynamics of encapsulation of local anesthetics into a liposome using the MARTINI forcefield. This study shed light on the assembly/adsorption mechanisms of small molecules to cellular membranes.
- At the highest scale, we concentrated on spherical colloids as the most effective way to date to model bio-polyelectrolytes in cells (DNA, proteins, ..). With Prof. Pagonabarraga, electrophoretic processes were studied with unprecedented detail with a Poisson-Boltzmann description coupled to lattice Boltzmann model to solve the hydrodynamics.
Research extending the capabilities of our computational framework was also pursued to enable code development on NVIDIA Graphics Processing Units. Apart from the scientific project impact, recognized by the publications produced and by the fact that at least three different groups are willing to collaborate and use the tools and knowledge created, its overall impact is foreseen to be relevant as it directly targets bio- and nano- technology (key research areas indicated by the EU) and has produced highly interdisciplinary results at the fundamental (electrophoresis, drug delivery) and technological (GPU computing) level. The scientist was invited to visit different research groups and also hosted researchers during the project. The broad echo of the project is demonstrated by the outstanding amount of multidisciplinar work that was executed, bringing together collaborators from different fields and by the fact that MacroMolecules At Work was chosen by EU to publish a comment for general readership in the Projects magazine, reaching out a wide audience well beyond scientific communities.