Input Files for REUS Free Energy Calculations of Loop Folding, G-tract Binding, and Propeller Loop Shift in G-Quadruplexes

This data set contains complete input files required to perform replica exchange umbrella sampling (REUS) simulations of three processes in G-quadruplex systems: (i) folding of isolated loops containing one to four thymine residues into defined loop geometries, (ii) binding of an unconnected G-tract to a preassembled G-core, and (iii) positional shift of a two-guanine G-tract between the upper and lower binding sites within a three-tetrad G-core scaffold in propeller loop geometries.
In the loop-folding simulations, the reaction coordinate is defined as the mean pairwise distance between atoms involved in the formation of Hoogsteen hydrogen bonds between the 3’-end loop-connected G-tract and its two neighboring G-tracts in the G-core. In the unconnected G-tract binding simulations, the same type of reaction coordinate monitors formation of Hoogsteen hydrogen bonds between the binding G-tract and the G-core, with separate systems corresponding to distinct glycosidic bond angle conformations. In the propeller loop shift simulations, the reaction coordinate is defined as the difference between the mean pairwise distances of hydrogen bond–forming atoms of the two-guanine G-tract to guanine bases in the upper versus lower binding site.
For each REUS window, the data set provides: (i) an initial structure extracted from nonequilibrium simulations spanning the relevant reaction-coordinate range, (ii) a PLUMED input file defining the reaction coordinate and umbrella bias together with structural restraints used to preserve the integrity of the G-core and the position of channel K+ ion(s), (iii) reference structure file(s) where required for RMSD-based definitions, and (iv) a compiled GROMACS .tpr file containing the full system topology and molecular dynamics parameters. All systems are fully solvated and include the preassembled G-core scaffold, the relevant loop or G-tract component, and K+ and Cl– ions at physiological concentration (150 mM).
The data set therefore enables reconstruction of free energy profiles for loop folding, G-tract binding, and propeller loop positional shift using consistent REUS protocols across all systems.