Ligand Binding and migration in heme proteins: an intrinsically multiscale problem

CAPECE, LUCIANA

Congreso; Reunion Anual de la Sociedad Argentina de Biofisica; 2021

Computer simulation studies of the molecular basis for ligand migration in proteins allow the description of key events such as the transition between docking sites, displacement of existing ligands and solvent molecules, and open/closure of specific "gates", among others. On the other hand, binding of external ligands is related to protein function, and usually can trigger conformational changes and allosteric transitions. In heme proteins, ligand migration from the solvent to the active site preludes the binding to the heme iron and is related to different functions. In particular, in human hemoglobin, binding of O2 to the heme iron preludes the T to R allosteric transition. In this talk I will present different computational strategies and models that we use in our group to study these processes in heme proteins, which range from QM/MM calculations to coarse grain simulations, and Markov State Models.