There is a growing interest in developing biomolecular coarse grained (CG) simulation methodologies. Usually, groups of atoms are clustered into new CG beads, typically between 10 and 20 atoms per bead. To move to higher time- and length-scales, we need simpler models with computationally efficient implementations. Fluctuating Finite Element Analysis (FFEA) is a recently proposed CG model treating globular proteins as a viscoelastic continua with thermal noise. Each protein is discretised into a tetrahedral mesh, parametrised locally by bulk continuum properties and short-range potentials that describe the interaction with other proteins. FFEA solves the stochastic equations of motion, computing trajectories for the time evolution of the system at the meso-scale. Low-resolution biomolecular structures, obtained using 3D cryo-electron microscopy and available in the public EMDataBank can be used directly.<br/><br/>We present an advance for the FFEA approach to model specific protein-protein interactions. We used a variation of the "force matching" method to to map all-atom forces, coming from molecular dynamics trajectories, onto basis functions representing the potential of mean force between different CG-site pairs. The resulting CG pair-pair potentials were introduced to the FFEA model. We applied this approach to simulate a fibrin monomer, a 45-nm protein responsible of forming a fibrin network, a key event in blood clot formation. After adjusting the Young's modulus for the fibrin monomer using data from forced unfolding single-molecule experiments, we obtained the FFEA trajectories at a low computational cost, validating the approach through comparison with electron microscopy experiments. We are working on an efficient parallel implementation suitable for the HPC infrastructure. This will open the door to simulate the fibrin network self-assembly process, as well as other large-scale molecular processes.

Bottom-up approach to describe protein-protein interactions in a continuum mechanics biomolecular model of fibrin

251st National Meeting (2016)

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