Applying coarse grain models to understand key molecular processes in hemoglobins

CAPECE, LUCIANA

Chicago

Congreso; ACS Fall 2022; 2022

American Chemical Society

As many other roads that were built in our lab in Buenos Aires, the coarse grain street was also initiated by Adrian. After my PhD, I had the chance to work with Adrian in Barcelona, while he was in his sabbatical year. In that occasion, when Prof. Javier Luque kindly hosted me in order to work in this project, I made my first steps in coarse grain (CG) simulations. Using a CG model developed originally by Voth et al., we developed a heme CG model in order to simulate heme proteins. This heme model was applied to different heme proteins, including the monomeric globins myoglobin (Mb) and neuroglobin (Ngb), and tetrameric human hemoglobin (Hb). Long-term equilibrium coarse-grained molecular dynamics were run showing that the structures are stable along the simulation and also retain qualitatively the flexibility patterns of the atomistic simulation. CG simulations are able to capture the difference between Mb and Ngb in their behaviour towards hexacoordination. We also applied this model to describe the allosteric transition between the R(Relaxed) and T(Tense) states in human hemoglobin, using a collective reaction coordinate. The CG model characterization is in very good agreement with the atomistic results, validating this scheme for the treatment of allosteric processes in heme proteins. Lately, we applied a different coarse grain Model (Sirah force field) for which we also developed a heme model, to simulate the interaction between a bacterial truncated hemoglobin and a biological membrane. The reduced scale of this simulations allowed us to obtain stable conformations of the protein-membrane complex which allows us to lately propose a molecular mechanism for oxygen affinity regulation due to the interaction with the membrane.