M. The and . Sklodowska-curie, This research was supported by the "Departments of Excellence-2018" Program (Dipartimenti di Eccellenza) of the Italian Ministry of Education

M. Benfatto, E. Pace, N. Sanna, C. Padrin, and G. Chillemi, MXAN and molecular dynamics: A new way to look to the XANES (X-ray absorption near edge structure) energy region, Multiple Scattering Theory for Spectroscopies, vol.204, pp.197-219, 2018.

M. Benfatto and C. A. Meneghini, Close look into the low energy region of the XAS spectra: The XANES region, Synchrotron Radiation, pp.213-240, 2015.

M. Benfatto and S. D. Longa, Geometrical fitting of experimental XANES spectra by a full multiple-scattering procedure, J. Synchrotron Radiat, vol.8, pp.1087-1094, 2001.

S. D. Longa, A. Arcovito, M. Girasole, J. L. Hazemann, and M. Benfatto, Quantitative analysis of X-ray absorption near edge structure data by a full multiple scattering procedure: The Fe-CO geometry in photolyzed carbonmonoxymyoglobin single crystal, Phys. Rev. Lett, vol.87, p.155501, 2001.

A. Arcovito, X-ray structure analysis of a metalloprotein with enhanced active-site resolution using in situ x-ray absorption near edge structure spectroscopy, Proc. Natl. Acad. Sci. U. S. A, vol.104, pp.6211-6216, 2007.

R. Sarangi, The x-ray absorption spectroscopy model of solvation about sulfur in aqueous L-cysteine, J. Chem. Phys, vol.137, p.205103, 2012.

E. Antonini and M. Brunori, Hemoglobin and Myoglobin in Their Reactions with Ligands, p.436, 1971.

H. Frauenfelder, B. H. Mcmahon, and P. W. Fenimore, Myoglobin: The hydrogen atom of biology and a paradigm of complexity, Proc. Natl. Acad. Sci. U. S. A, vol.100, pp.8615-8617, 2003.

J. S. Olson, The role of the distal histidine in myoglobin and haemoglobin, Nature, vol.336, pp.265-266, 1988.

M. F. Perutz and F. S. Mathews, An X-ray study of azide methaemoglobin, J. Mol. Biol, vol.21, pp.199-202, 1966.

M. Brunori, Myoglobin strikes back, Protein Sci, vol.19, pp.195-201, 2010.

J. B. Wittenberg, Myoglobin function reassessed, J. Exp. Biol, vol.206, 2003.

A. Tomita, U. Kreutzer, S. Adachi, S. Koshihara, and T. Jue, It's hollow': The function of pores within myoglobin, J. Exp. Biol, vol.213, pp.2748-2754, 2010.

C. Bossa, Extended molecular dynamics simulation of the carbon monoxide migration in sperm whale myoglobin, Biophys. J, vol.86, pp.3855-3862, 2004.

G. Hummer, F. Schotte, and P. A. Anfinrud, Unveiling functional protein motions with picosecond x-ray crystallography and molecular dynamics simulations, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.15330-15334, 2004.

D. R. Nutt and M. Meuwly, CO migration in native and mutant myoglobin: Atomistic simulations for the understanding of protein function, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.5998-6002, 2004.

L. Maragliano, G. Cottone, G. Ciccotti, and E. Vanden-eijnden, Mapping the network of pathways of CO diffusion in myoglobin, J. Am. Chem. Soc, vol.132, pp.1010-1017, 2010.

R. Elber and M. Karplus, Multiple conformational states of proteins: A molecular dynamics analysis of myoglobin, Science, vol.235, pp.318-321, 1987.

M. Anselmi, A. D. Nola, and A. Amadei, The kinetics of ligand migration in crystallized myoglobin as revealed by molecular dynamics simulations, Biophys. J, vol.94, pp.4277-4281, 2008.

L. U. Brinkmann and J. S. Hub, Ultrafast anisotropic protein quake propagation after CO photodissociation in myoglobin, Proc. Natl. Acad. Sci. U. S. A, vol.113, pp.10565-10570, 2016.

T. R. Barends, Direct observation of ultrafast collective motions in CO myoglobin upon ligand dissociation, Science, vol.350, pp.445-450, 2015.

D. R. Nutt and M. Meuwly, Theoretical investigation of infrared spectra and pocket dynamics of photodissociated carbonmonoxy myoglobin, Biophys. J, vol.85, pp.3612-3623, 2003.

. Chillemi, Struct. Dyn, vol.5, p.54101, 2018.

D. R. Nutt and M. Meuwly, Ligand dynamics in myoglobin: Calculation of infrared spectra for photodissociated NO, ChemPhysChem, vol.5, pp.1710-1718, 2004.

M. Meuwly, On the influence of the local environment on the CO stretching frequencies in native myoglobin: Assignment of the B-states in MbCO, ChemPhysChem, vol.7, pp.2061-2063, 2006.

M. Anselmi, M. Aschi, A. D. Nola, and A. Amadei, Theoretical characterization of carbon monoxide vibrational spectrum in sperm whale myoglobin distal pocket, Biophys. J, vol.92, pp.3442-3447, 2007.

C. Oostenbrink, A. Villa, A. E. Mark, and W. F. Van-gunsteren, A biomolecular force field based on the free enthalpy of hydration and solvation: The GROMOS force-field parameter sets 53A5 and 53A6, J. Comput. Chem, vol.25, pp.1656-1676, 2004.

C. , Heme distortions in sperm-whale carbonmonoxy myoglobin: Correlations between rotational strengths and heme distortions in MD-generated structures, J. Am. Chem. Soc, vol.124, pp.3385-3394, 2002.

E. R. Henry, M. Levitt, and W. A. Eaton, Molecular dynamics simulation of photodissociation of carbon monoxide from hemoglobin, Proc. Natl. Acad. Sci. U. S. A, vol.82, pp.2034-2038, 1985.

J. W. Petrich, Ligand binding and protein relaxation in heme proteins: A room temperature analysis of nitric oxide geminate recombination, Biochemistry (Mosc.), vol.30, pp.3975-3987, 1991.

D. A. Case and M. Karplus, Stereochemistry of carbon monoxide binding to myoglobin and hemoglobin, J. Mol. Biol, vol.123, pp.697-701, 1978.

X. Y. Li and T. G. Spiro, Is bound carbonyl linear or bent in heme proteins? Evidence from resonance Raman and infrared spectroscopic data, J. Am. Chem. Soc, vol.110, pp.6024-6033, 1988.

F. A. Lima, Probing the electronic and geometric structure of ferric and ferrous myoglobins in physiological solutions by Fe K-edge absorption spectroscopy, Phys. Chem. Chem. Phys, vol.16, pp.1617-1631, 2014.

G. Chillemi, E. Pace, M. D'abramo, and M. Benfatto, Equilibrium between 5-and 6-fold coordination in the first hydration shell of Cu(II), J. Phys. Chem. A, vol.120, pp.3958-3965, 2016.

M. Antalek, Solvation structure of the halides from x-ray absorption spectroscopy, J. Chem. Phys, vol.145, p.44318, 2016.

P. Angelo, O. M. Roscioni, G. Chillemi, S. D. Longa, and M. Benfatto, Detection of second hydration shells in ionic solutions by XANES: Computed spectra for Ni 2þ in water based on molecular dynamics, J. Am. Chem. Soc, vol.128, pp.1853-1858, 2006.

P. Angelo, Dynamic investigation of protein metal active sites: Interplay of XANES and molecular dynamics simulations, J. Am. Chem. Soc, vol.132, pp.14901-14909, 2010.

G. Chillemi, Carbon monoxide binding to the heme group at the dimeric interface modulates structure and copper accessibility in the Cu, Zn superoxide dismutase from Haemophilus ducreyi: In silico and in vitro evidences, J. Biomol. Struct. Dyn, vol.30, pp.269-279, 2012.

T. A. Tyson, K. O. Hodgson, C. R. Natoli, and M. Benfatto, General multiple-scattering scheme for the computation and interpretation of x-ray-absorption fine structure in atomic clusters with applications to SF 6 , GeCl 4 , and Br 2 molecules, Phys. Rev. B, vol.46, pp.5997-6019, 1992.

F. James and M. Roos, Minuit -A system for function minimization and analysis of the parameter errors and correlations, Comput. Phys. Commun, vol.10, pp.343-367, 1975.

M. Benfatto and S. D. Longa, MXAN: New improvements for potential and structural refinement, J. Phys.: Conf. Ser, vol.190, p.12031, 2009.

K. Kuczera, J. Kuriyan, and M. Karplus, Temperature dependence of the structure and dynamics of myoglobin, J. Mol. Biol, vol.213, pp.351-373, 1990.

F. Autenrieth, E. Tajkhorshid, J. Baudry, and Z. Luthey-schulten, Classical force field parameters for the heme prosthetic group of cytochrome c, J. Comput. Chem, vol.25, pp.1613-1622, 2004.

S. Adam, M. Knapp-mohammady, J. Yi, and A. Bondar, Revised CHARMM force field parameters for ironcontaining cofactors of photosystem II, J. Comput. Chem, vol.39, pp.7-20, 2018.

M. Soloviov, A. K. Das, and M. Meuwly, Structural interpretation of metastable states in myoglobin-NO, Angew. Chem., Int. Ed, vol.55, pp.10126-10130, 2016.

M. Anselmi, M. Brunori, B. Vallone, and A. D. Nola, Molecular dynamics simulation of deoxy and carboxy murine neuroglobin in water, Biophys. J, vol.93, pp.434-441, 2007.

C. I. Bayly, P. Cieplak, W. Cornell, and P. A. Kollman, A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model, J. Phys. Chem, vol.97, pp.10269-10280, 1993.

C. M. Breneman and K. B. Wiberg, Determining atom-centered monopoles from molecular electrostatic potentials. The need for high sampling density in formamide conformational analysis, J. Comput. Chem, vol.11, pp.361-373, 1990.

A. D. Becke, Density-functional thermochemistry. III. The role of exact exchange, J. Chem. Phys, vol.98, pp.5648-5652, 1993.

C. Lee, W. Yang, and R. G. Parr, Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Phys. Rev. B, vol.37, pp.785-789, 1988.

M. J. Frisch, , 2016.

G. S. Kachalova, A. N. Popov, and H. D. Bartunik, A steric mechanism for inhibition of CO binding to heme proteins, Science, vol.284, pp.473-476, 1999.

S. Pronk, GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit, Bioinformatics, vol.29, pp.845-854, 2013.

R. B. Best, Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone /, w and side-chain v 1 and v 2 dihedral angles, J. Chem. Theory Comput, vol.8, pp.3257-3273, 2012.

B. P. Hess, LINCS: A parallel linear constraint solver for molecular simulation, J. Chem. Theory Comput, vol.4, pp.116-122, 2008.

T. Darden, D. York, and L. Pedersen, Particle mesh Ewald: An N Álog (N) method for Ewald sums in large systems, J. Chem. Phys, vol.98, pp.10089-10092, 1993.

G. Bussi, D. Donadio, and M. Parrinello, Canonical sampling through velocity rescaling, J. Chem. Phys, vol.126, p.14101, 2007.

. Chillemi, Struct. Dyn, vol.5, p.54101, 2018.

H. J. Berendsen, J. P. Postma, W. F. Van-gunsteren, A. Dinola, and J. R. Haak, Molecular dynamics with coupling to an external bath, J. Chem. Phys, vol.81, pp.3684-3690, 1984.

M. O. Krause and J. H. Oliver, Natural widths of atomic K and L levels, K a X-ray lines and several K L L Auger lines, J. Phys. Chem. Ref. Data, vol.8, pp.329-338, 1979.

J. Vojt-echovsk-y, K. Chu, J. Berendzen, R. M. Sweet, and I. Schlichting, Crystal structures of myoglobin-ligand complexes at near-atomic resolution, Biophys. J, vol.77, pp.2153-2174, 1999.

L. Tofani, Spectroscopic and interfacial properties of myoglobin/surfactant complexes, Biophys. J, vol.87, pp.1186-1195, 2004.

J. B. Asbury, T. Steinel, and M. D. Fayer, Hydrogen bond networks: Structure and evolution after hydrogen bond breaking, J. Phys. Chem. B, vol.108, pp.6544-6554, 2004.

K. Nienhaus, J. S. Olson, S. Franzen, and G. U. Nienhaus, The origin of stark splitting in the initial photoproduct state of MbCO, J. Am. Chem. Soc, vol.127, pp.40-41, 2005.

. Chillemi, Struct. Dyn, vol.5, p.54101, 2018.