Multiscale modelling of squid inspired tandem repeat proteins

Official URL: https://risc01.sabanciuniv.edu/record=b2486289 _(Table of Contents)

Squid ring teeth (SRT) proteins are structural proteins with repetitive amino acid sequences. They comprise two regions which are crystal forming and tie-chain regions. The mechanical properties of the protein known however the exact mechanism for the aggregation of the protein between the previously mentioned segments are still unknown. SRT proteins have unknown folding behavior and the size of those synthesized to date vary between 140 to 875 for a single chain. Considering these factors, we used Dissipative Particle Dynamics (DPD) simulations as our primary method of simulations rather than only using Molecular Dynamics (MD) simulations since MD simulations would be computationally expensive. So, in this study, we propose a method, which was previously used in polymers, of parameterizing the SRT proteins via multiscale simulations. To parameterize the system, we initially used binary MD simulations of each bead pair in the system at the atomistic detail. Then, we coarse-grained all the molecules into beads, and using the cohesive energy density values from the MD simulations, we constructed FloryHuggins interaction parameters for all pairs in our system. We used four varying sizes of SRT proteins, n4, n7, n11, and n25 and two different solvents which were the good solvent HFIP and the hypothetical poor solvent P. Radial distribution function and structure factor calculations were used to characterize the structure of the SRT proteins in specified solvents. The results show that the SRT proteins swell in HFIP and they have no long-range order, but they cluster and form ordered structures in solvent P which show that the computational results agree with the experimental data