The association of ligands to proteins is regulated by interactions between the molecule and protein residues at the binding site, which can be located in a binding pocket or on the protein surface.
Such interactions can directly modulate protein functions and conformations, with possible implications for biophysical processes such as protein co-crystallisation [1-3] or selective molecular design [4].
Computational methods to study these systems, as molecular dynamics simulations (MDs) which can range from atomistic to coarse-grained resolution [5,6], provide insights into the mechanisms, kinetics and thermodynamics underlying protein-ligand complex formation.

Here, it will be discussed how these supramolecular structures may be described by these approaches, highlighting characteristic fingerprints and key models for interactions.

[1] McGovern, R.E., Fernandes, H., Khan, A.R., Power, N.P., Crowley, P.B. Nat. Chem. 4, 527-533 (2012)
[2] Bartocci, A., Pereira, G.P., Cecchini, M., Dumont, E. JCIM 62, 6739-6748 (2022)
[3] Bartocci, A., Dumont, E. J. Chem. Phys. 160, 105101 (2024)
[4] Heinzelmann, G., Henriksen, N.M., Gilson, M.K. JCTC 13, 3260-3275 (2017)
[5] Marrink, S.J., Risselada, H.J., Yefimov, S., Tieleman, D.P., de Vries, A.H. J. Phys. Chem. B 111, 7812-7824 (2007)
[6] Souza, P.C.T., Thallmair, S., Conflitti, Ramírez-Palacios, P.C., Alessandri, R., Raniolo, S., Limongelli, V., Marrink, S.J. Nat. Comm. 11, 1-11 (2020)