Computational protocol: Biomimetic temporal self-assembly via fuel-driven controlled supramolecular polymerization

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[…] Calculation of atomic site charges: To carry out the MM/MD simulations of oligomers of either ATP-1 or GTP-1 in solution, the atomic site charges of either system have to be determined. The procedure to obtain the same is described below.Firstly, a dimer configuration (a total of 291 atoms) was constructed using GaussView software as shown in Supplementary Fig. . Density functional theory (DFT) calculations were performed using the QUICKSTEP module in CP2K software. All valence electrons were treated in a mixed basis set with energy cutoff of 280 Ry. The short-range version of the double zeta single polarization basis set was used. The effect of core electrons was taken through pseudopotentials of Goedecker–Tetter–Hutter (GTH). The Perdew–Burke–Ernzerhof (PBE) exchange and correlation functional was employed. DFT-D3 corrections were used to take van der Waals interactions into account and the dimer geometry was optimized in gas phase. The initial and final configurations of this gas phase dimer are shown in Supplementary Fig. , respectively.A dimer of ATP-1 has three parts: the OPV region, the DPA region, and the ATP. The phosphates of one ATP molecule can bind to two zinc atoms of two different molecules of 1. A model of the oligomer wherein each ATP binds two adjacent molecules of 1 in the stacking direction would satisfy the two critical experimental observations: (a) the ends of the supramolecular polymer has free receptor sites to drive a “living” growth in presence of additional ATP and (b) the ATP to 1 mole ratio between 0.9 and unity. A schematic of such a model used for the MM/MD simulations is illustrated in Supplementary Fig. . The molecular structure of such a dimer is shown in Supplementary Fig. . Out of the four DPA receptor moieties in ATP-1 dimer, two are bound to one ATP molecule, while the other two are free. Thus, the atomic site charges on either ends of ATP-1 dimer will differ. Thus ATP-1 (or GTP-1) oligomer will have both ATP-bound DPA ends as well as free (unbound) DPA receptor ends. Hence the force field has to have different charges on the backbone of 1 to take into account these structural differences. Supplementary Fig. a displays these different segments in ATP-1 dimer, using which higher oligomers can be constructed. The atomic site charges for each segment in the dimer was determined through the DDEC/c3 method, using the electronic densities obtained via DFT calculation of the dimer, as described above. These segments were then fused to obtain site charges for higher oligomers. The procedure for such a construction is illustrated for the cases of trimer and hexamer in Supplementary Fig. b and c, respectively. The atom mapping scheme is provided in Supplementary Fig.  and the corresponding values of the charges on atoms of dimer are provided in Supplementary Tables –. [...] MD simulations were performed in all-atom representation. Molecule 1, ATP, GTP, and counter ions were modelled using the DREIDING force field. Water, used as solvent was modelled using the TIP3P force field. Cross-interactions between the solute and solvent were considered through DREIDING mixing rules. A pseudo bond between Zinc and sp3-hybridized nitrogen atom of DPA was created, with equilibrium bond length 2.2 Å, which was chosen from studying crystal structure of similar compounds. Necessary number of counterions (Cl−) were added to the solution containing oligomers to attain charge neutrality. ATP-1 oligomers containing the following number of OPV moieties were simulated in solution: 2, 3, 4, 6, 10, 15, and 25. For the case of GTP-1, only the 25-mer was studied. The initial configuration of the 25-mer of both ATP-1 and GTP-1 are shown in Supplementary Fig. . Details of the system sizes employed in MM/MD simulations of all oligomers are provided in Supplementary Table .MD simulations were performed using LAMMPS package at 298.15 K in the constant temperature and constant pressure ensemble. The Nosé-Hoover chain thermostat was used to maintain constant temperature and Nosé-Hoover barostat used to maintain constant pressure with a coupling constant of 1 ps. Three-dimensional periodic boundary conditions were employed. Non-bonded interactions were truncated at distance of 12 Å. Particle–particle particle–mesh (PPPM) solver was used to consider the long-range interactions. The equations of motion were integrated using the velocity Verlet integrator with a timestep of 0.5 fs. The coordinates of the molecules were stored for post-processing every 2.5 ps and the trajectory was visualized using VMD. In every simulation, the preformed oligomer was solvated in water using Packmol.All MM/MD simulations of all the small oligomers were carried out for duration of 30 and 60 ns for 25-mer in GTP-1 or ATP-1 system. While the first 5 ns of the trajectory was used for equilibration, the structural analyses reported here were obtained from the last 25 ns of the trajectory for small oligomer size and last 55 ns for 25-mer. […]

Pipeline specifications

Software tools GaussView, LAMMPS, VMD
Applications Drug design, Protein structure analysis