Goal 1: To acquire an initial list of candidate ICC structures from the Protein Data Bank.



In order to decide which candidates to expand, all available PDB files were fed into a series of Python scripts to isolate feasible units. Feasibility criterion included proper number of alpha carbons, correct number of oxygen prime atoms, and ideal symmetry with respect to DNA protein alignment. With a list of expandable units, the next step was to calculate the most ideal expansion size.



Goal 2: To establish DNA insert sizes for creating output model files of priority candidates in Pymol. These priority candidates will be used in GROMACs simulations.



To find the optimal DNA strut insert for expansion, the root-mean-square deviation (RMSD) needed to be minimized. For each candidate, the RMSD was calculated for a range of DNA strut sizes between 4-40 base pairs. The base pair inserts that correlated with minimized RMSD’s were considered to be optimal for insertion.

With each candidate having the respective DNA insert size, a Pymol model was created showing each candidate in an expanded form.




Goal 3: To successfully use GROMACs software to  run molecular dynamic (MD) simulations on ICC crystal designs with expanded DNA struts of varying sizes to determine relative stabilities.


The Pymol expanded models enabled a GROMACS simulation to be produced for each candidate.

The RMSD of alpha carbons was analyzed for the duration of the simulations to see the total movement of molecules. Specific atoms were involved in hydrogen bonding in the sticky overhang section of the extended DNA struts. GROMACSAs these interactions are likely the weakest point in the molecule, several simulations were run to determine the breaking point for these interactions. These simulations provided a “benchmark” point for stability.

RMSD data was combined with the hydrogen bond breaking point to give empirical data to help determine relative stabilities between base pair insert sizes.



Goal 4: To create educational Pymol videos describing our experimental process.


We have created educational Pymol series explaining our isoreticular co-crystal design and applications.