Stationary and Time-Dependent Carbon Monoxide Stretching Mode Features in Carboxy Myoglobin: A Theoretical–Computational Reappraisal

Abstract

The stationary and time-dependent infrared spectrum (IR) of the CO stretching mode (νCO) in carboxymyoglobin (MbCO), a longstanding problem of biophysical chemistry, has been modeled through a theoretical–computational method specifically designed for simulating quantum observables in complex atomic–molecular systems and based on a combined application of long time scale molecular dynamics simulations and quantum-chemical calculations. This study is basically focused on two aspects: (i) the origin of the stationary IR substates (termed as A 0, A 1, and A 3) and (ii) the modeling and the interpretation of the νCO energy relaxation. The results, strengthened by a more than satisfactory agreement with the experimental data, concisely indicate that (i) the conformational His64-FeCO relevant substates, i.e., characterized by the formation-disruption of the H-bond between the above moieties, are the main responsible of the presence of two distinct and well separated (A 0 and A 1/A 3) spectroscopic regions; (ii) the characteristic bimodal shape of the A 1/A 3 spectral region, according to our model, is the result of the fluctuation of the electric field pattern as provided by the protein–solvent framework perturbing the bound His64-CO-Heme complex; and (iii) the electric field pattern, in conjunction with the relatively high density of MbCO vibrational states, is also the main determinant of the νCO energy relaxation, characterizing its kinetic efficiency.

CO bonding in hexa‐ and pentacoordinate carboxy‐neuroglobin: A quantum mechanics/molecular mechanics and local vibrational mode study

“…For bonded ligands in the wild type sperm whale MbCO, four different substates related to CO stretching vibrations denoted as A 0 , A 1 , A 2 and A 3 (with the frequencies of a value of 1965, 1947, 1942, and 1932 cm −1 , respectively) were observed 209–212 . The protein substates were assigned to His64–open and closed conformational states as well as local effects of the amino acids, different sizes of the cavities, or certain interactions between His64 and FeCO 213–217 . It has been suggested that the differences observed among the various CO stretching conformers stem from changes in the electrostatic interaction between the heme pocket and the CO that is coordinated to the Fe atom of the heme group 218 .…”

“…For MbCO it is widely recognized that substates A 0 and A 1 correspond to the His64–open and closed conformational states while the origin of substate A 3 has been a highly debated subject; some investigations having proposed the following to explain its origin: (1) the local field– effect enabled by amino acids, (2) differing size of the cavities, (3) certain interactions between His64 and FeCO 213–216 . However, more recent work has revealed that the origin of A 3 , as well as A 0 and A 1 , is solely attributed to the H–bond interaction between FeCO and His64 that, in turn, result in the His64–open and closed conformations; the free energy difference between the two conformations was found to be between 4 and 5 kJ/mol 217 . It also has been speculated that different protein conformations of varying substates, various mutations, and the presence of solvent near prosthetic groups may govern the time it takes for the excited state of the CO stretching mode in MbCO to reach the lowest excited vibrational state 223,224 …”

“…[209][210][211][212] The protein substates were assigned to His64-open and closed conformational states as well as local effects of the amino acids, different sizes of the cavities, or certain interactions between His64 and FeCO. [213][214][215][216][217] It has been suggested that the differences observed among the various CO stretching conformers stem from changes in the electrostatic interaction between the heme pocket and the CO that is coordinated to the Fe atom of the heme group. 218 Moreover, because H64 can take on two tautomer forms, the interaction with the CO ligand coordinated to the Fe varies, and which tautomer form is the most stable often remains unclear.…”

“…[213][214][215][216] However, more recent work has revealed that the origin of A 3 , as well as A 0 and A 1 , is solely attributed to the H-bond interaction between FeCO and His64 that, in turn, result in the His64-open and closed conformations; the free energy difference between the two conformations was found to be between 4 and 5 kJ/mol. 217 It also has been speculated that different protein conformations of varying substates, various mutations, and the presence of solvent near prosthetic groups may govern the time it takes for the excited state of the CO stretching mode in MbCO to reach the lowest excited vibrational state. 223,224 Other studies have suggested that strengthening of the FeC bonding in MbCO and it mutations leads to a weakening of the CO sis.…”

Theoretical–Computational Modeling of CD Spectra of Aqueous Monosaccharides by Means of Molecular Dynamics Simulations and Perturbed Matrix Method

“…It is important to emphasize two key aspects of the method: (i) as compared to the typical quantum mechanic/molecular mechanic (QM/MM) methods [46], the QC and the rest of the system are simulated using the same Hamiltonian (typically. empirical force fields); (ii) the above definition of the QC, i.e., the simplest, in some cases, might be not suitable [47], and in these cases, its definition should be addressed critically and according to the problem at hand. More explicitly, the computational strategy of PMM is based on the a posteriori evaluation at each frame of the MD trajectory of the electronic and magnetic properties of the QC, along with the rest of the system, i.e., the solvent, acting as an electrostatic perturbation.…”