In this seminar I will talk about the procedure of structural determination using the methods of nuclear magnetic resonance spectroscopy. The structure to be determined is the drug-resistant mutant of the rapamycin binding domain of the mTOR kinase, which belongs to the mTORC1/mTORC2 complexes. Rapamycin, a macrolide drug that possesses immunosuppressive and anti-proliferative properties, has also been used as an artificial trigger to modulate genetically engineered reaction networks, and its derivatives have been approved for clinical use between in graft transplant and oncology. Recently we have combined nuclear magnetic resonance (NMR), single-molecule force spectroscopy (SMFS), and molecular dynamics (MD), to acquire a multi-timescale view of the interactions among the FKBP12-rapamycin-FRB ternary complex. We will demonstrate how the structural changes in the drug-resistant mTOR mutant influence the binding of rapamycin, thereby identifying the key interactions for maintaining the ternary complex. Specifically, how different mutants in the two proteins FKBP12 and FRB affect the interactions in this ternary complex were investigated with these approaches in a cohesive manner. We extensively applied our recently developed curvilinear-path umbrella sampling (CPUS) approach to estimate the standard free energy of binding and to characterize the curvilinear dissociation physical trajectories of this ternary complex. We anticipate that our investigations will be beneficiary for future design of rapamycin analogs (rapalogs).