Cyclosporines - Molecular Dynamics Files

Cyclosporine A, a cyclic undecapeptide, and many of its analogs display sufficient passive membrane permeability despite several violations of Lipinski's rule-of-five for bioavailability. We explore this beyond-the-rule-of-five space of molecules closely related to cyclosporine with a series of experimental and computational techniques in hope of elucidating structure-property relationships manifesting from side-chain substitutions and epimerizations. Herein, we perform temperature-replica exchange calculations of our modifications to cyclosporine at its first residue, (E)-2-Butenyl-4-methyl-threonine and demonstrate a disruption in the presence of the major aqueous conformation. Trajectories of constant-temperature runs at 311.61 are included with topology and input files.