Startseite Metal–ligand bonding and noncovalent interactions of mutated myoglobin proteins: a quantum mechanical study
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Metal–ligand bonding and noncovalent interactions of mutated myoglobin proteins: a quantum mechanical study

  • Juliana J. Antonio und Elfi Kraka ORCID logo EMAIL logo
Veröffentlicht/Copyright: 4. September 2025
Pure and Applied Chemistry
Aus der Zeitschrift Pure and Applied Chemistry

Abstract

Metal–ligand bonding and noncovalent interactions (NCIs), such as hydrogen bonding or π–π interactions, play a crucial role in determining the structure, function, and selectivity of both biological and artificial metalloproteins. In this study, we employed a hybrid quantum mechanics/molecular mechanics (QM/MM) approach to investigate the ligation of water or cyanide in a mutated myoglobin system, in which the native heme scaffold was replaced with M-salophen or M-salen Schiff base complexes (M = Cr, Mn, Fe). Using our local vibrational mode analysis, particularly local vibrational mode force constants as intrinsic bond strength parameters, complemented with electron density and natural orbital analyses we explored the role of metal–ligand bonding and NCIs in different environments within the myoglobin pocket. Our analysis revealed that metal–ligand bonding, for both water and cyanide ligands, is strongest in the delta form of distal histidine and favors salophen prosthetic groups, as indicated by an overall increase in metal–ligand bond strength. Hydrogen bonding between the distal histidine and ligand also exhibited greater strength in the delta form; however, this effect was more pronounced with salen prosthetic groups. Additionally, the NCIs within the active pocket of the protein were found to be variable, highlighting the adaptability of local force constants. In summary, our data underscore the potential of computational methodologies in guiding the rational design of artificial metalloproteins for tailored applications, with local vibrational mode analysis serving as a powerful tool for bond strength assessment.

Keywords: π-π interactions; hydrogen bonding; local vibrational force constants; local vibrational mode analysis; metal–ligand bonding; myoglobin; non-covalent interactions; QM/MM; quantum science and technology
Corresponding author: Elfi Kraka, Department of Chemistry, Computational and Theoretical Chemistry Group (CATCO), Southern Methodist University, 3215 Daniel Ave, Dallas, TX 75275-0314, USA, e-mail:
Article note: A collection of invited papers to celebrate the UN’s proclamation of 2025 as the International Year of Quantum Science and Technology.

Funding source: National Science Foundation, NSF

Award Identifier / Grant number: CHE2102461

Award Identifier / Grant number: DGE-2034834

Acknowledgments

Computational resources provided by SMU’s O’Donnell Institute of Data Science and High Performance Computing.

  1. Research ethics: Not applicable.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: All other authors state no conflict of interest.

  6. Research funding: This work was supported by the National Science Foundation, Grant CHE2102461, and the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-2034834.

  7. Data availability: All data are available via the manuscript and/or the supporting Information.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/pac-2025-0454).

Received: 2025-03-06
Accepted: 2025-06-03
Published Online: 2025-09-04

© 2025 IUPAC & De Gruyter

https://doi.org/10.1515/pac-2025-0454
Schlagwörter für diesen Artikel
π-π interactions; hydrogen bonding; local vibrational force constants; local vibrational mode analysis; metal–ligand bonding; myoglobin; non-covalent interactions; QM/MM; quantum science and technology
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