Molecular simulations of globins: Exploring the relationship between structure, dynamics and function

The discovery in the last two decades of novel members of the globin superfamily has challenged the conventional view about the structure and function of globins. Thus, peculiar structural differences are expected to have direct influence on properties related to ligand migration, binding affinity and heme reactivity. Molecular simulations are a valuable tool to gain insigth into the molecular mechanisms that underlie those structural differences, and their relationship with the diversity of functional roles. In this work, the impact of molecular simulations in exploring Correspondence/Reprint request: Dr. F. J. Luque, Departament de Fisicoquimica, Facultat de Farmacia Universitat de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain. E-mail: fjluque@ub.edu Dr. D. Estrin Departamento de Quimica Inorganica, Analitica y Quimica Fisica, INQUIMAE-CONICET Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina E-mail: dario@qi.fcen.uba.ar Flavio Forti et al. 134 the linkage between structure, dynamics and function is highlighted for three representative cases: the migration of ligands through the protein matrix of truncated hemoglobins, the modulation of binding affinity by heme distortion in protoglobin, and finally the functional implications due to the equilibrium between pentaand hexacoordination of the heme with distal histidine in neuroglobin.