The dataset provides supporting information to a hypothesis of coded Cys being thermodynamically superior to non-coded homoCys and thioGly analogues. The results were first presented at the 30/80 Chemobrionics 2019 meeting in Granada, Spain (www.chemobrionics.eu) and the corresponding publication appears in the thematic issue Frontiers Interface RSC journal. The data set organized accordingly to the published figures and tables. Folders starting with numbers correspond to figures in the paper. The force field key files are to be used in combination of the amber99sb.prm force field, as provided by the Tinker 8.7 (dasher.wustl.edu/tinker/). The full secondary structure analysis was carried out using our in-house code (10.5281/zenodo.1442864). The folder 'trajectories' contains the peptides without the waterbath, while the 'waterbath' folder has the NPT equilibrated 6 nm waterbath in truncated octahedron geometry. The files starting with thermodynamics in the top folder has the numerical results used for calculating the cluster stability and ligand exchange reaction energetics. The folders 'reference cubane' and 'maquette with short peptides' contains the spin-polarized, ferro and antiferro-magnetically coupled electronic structure for all [4Fe-4S] cluster complexes. The key for the file extensions is as follows: FCHK: formatted Gaussian16 checkpoint file with spin polarized wave function KEY: Tinker control keyword file LOG: output file generated by a computer code LST: clear text file with the content of a compressed tar archive MSV: Discovery Studio Viewer Pro 5.0 binary file MD5: file checksum according to MD5 protocol ODS: Open Office electronic spreadsheet file PDW: PsiPlot data file PDB: Protein Databank Files PGW: PsiPlot graphics file PRM: Tinker force field parameter file TGZ: compressed tar archive TXT: clear text file or raw data set TXYZ: Tinker XYZ file with atomic, positions, atom types, and connectivity XYZ: Xmol file with atomic positions in Cartesian coordinates

Computations were carried out on the Hyalite High Performance Computing System, operated and supported by University Information Technology Research Cyberinfrastructure at Montana State University, Bozeman, MT. This work was supported by the National Science Foundation, Chemistry of Life Processes program, Grant #1609557.