Biological Molecular Dynamics Simulations 2.0

The project aims to promote molecular dynamics simulation of biological systems to the next level in three steps. At first, force field parameters of diverse post-translational modifications will be established both at all-atom and at coarse-grained resolution. The biological impact on molecular level of those post-translational modifications will be investigated on sample applications including cellular signalling events and interactions among bio(macro)molecules in cancerogenous cells. Next, a methodology for constant pH molecular dynamic simulations (both all-atom and coarse-grained) will be extended to diverse charged groups including titratable post-translational modification. This will allow for unravelling the role of charge adaptation in biological processes including protein insertion into cellular membranes, signal propagation within a cell, transmembrane transport and aggregation of biomolecules. In the last task a novel resolution conversion method will be developed based on automated generation of the mapping files by using machine learning and chemical information included e.g. in the original all- atom resolution. Therefore, the simulation system will be able to alter the resolution of the description between atomistic and coarse-grained resolution of diverse granularity in an automated manner thus sparing user-required time and avoiding user-induced errors. This technique will interconnect MD methods of diverse resolution by enabling sequential multiscaling MD simulations. However, not being restricted to biological systems, the fine-grading method will complement coarse graining techniques by a feedback control enabling a quality check of the newly established coarse-grained representation by its conversion back to higher level of resolution and control of the properties against experimental and other simulational data.