Presenter: Abhilash Sahoo (University of Maryland)
Topic: Water-Explicit Polarizable Coarse-Grained Model For Simulations with Proteins
The application of classical molecular dynamics (MD) simulations at atomic resolution (fine-grained level – FG), to the majority of biomolecular processes, remains limited because of the associated computational complexity of representing all the atoms. This problem is magnified in the presence of protein-based biomolecular systems that have a large conformational space and MD simulations at fine-grained resolution have slow dynamics to explore this space. Current transferrable coarse-grained (CG) force fields in literature are either limited to only peptides with the environment encoded in an implicit form (cannot study environmental heterogeneity) or cannot capture transitions into secondary/tertiary peptide structures from a primary sequence of amino acids. To address these constraints, we have developed a polarizable CG forcefield with an explicit representation of the environment for simulations with proteins. The forcefield consists of a set of pseudo-atoms representing different chemical groups that can be associated together to create different biomolecular systems. Here, we introduced explicit electronic polarization into the forcefield by augmenting the protein model with auxiliary drude-type charges. The non-bonded interactions are derived by fitting the parameters to reproduce experimentally observed and simulation-derived free energies. The bonded potentials are inferred from corresponding distributions in non-redundant protein structure databases. This CG model is transferable across a range of biomolecular systems and can be used in conjunction with the widely popular MARTINI CG model. We have validated our CG forcefield with simulations of well-studied aqueous and membrane protein systems. In this talk, I will discuss the CG model parametrization, validations and applications of the model and its previous iterations to study neurodegenerative protein aggregation in presence of model membranes and other co-solutes.