Theoretical modeling of the heme group with a hybrid QM/MM method

Maréchal, Jean‐Didier; Barea, Guada; Maseras, Feliu; Lledós, Agustı́; Mouawad, Liliane; Pérahia, David

doi:10.1002/(sici)1096-987x(200003)21:4<282::aid-jcc4>3.0.co;2-l

Cited by 35 publications

(5 citation statements)

References 60 publications

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“…The modelling of a porphyrin ring by two amidinato ligands has been previously used in theoretical calculations,21h23 and Ðnds experimental support in the activity of some non-heme FeII metal sites.28 We are also currently carrying out a systematic study on tetra-, penta-and hexacoordinated heme systems to prove the general validity of this modeling. 29 Although hybrid methods have a long story in the Ðeld of theoretical biochemistry,30 their previous applications have been mostly concentrated on the MM introduction of solvent e †ects on the di †erent features of a solute described at the QM level, with the usual application of molecular dynamics. The application presented in this paper is original in the sense that the QM/MM separation is within the studied molecule, which could not be otherwise described at the high computational level required.…”

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confidence: 99%

Binding of dioxygen in a picket-fence porphyrin complex of iron. A theoretical QM/MM study

Maseras¹

1998

New J. Chem.

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confidence: 99%

Binding of dioxygen in a picket-fence porphyrin complex of iron. A theoretical QM/MM study

Maseras¹

1998

New J. Chem.

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Section: Chorismate Mutasementioning

confidence: 99%

“…Another canonical group of proteins where valuable information can be obtained with QM/MM calculations are metalloproteins, whose functions typically involve reactive processes and electronic density rearrangements. Among them, heme proteins, the family of proteins containing an iron–porphyrin complex as a prosthetic group, were widely studied using QM/MM methodologies, especially in order to obtain information on ligand binding ,, and catalysis. ,, Particularly the globin family is one of the most studied, including the well-known mammalian hemoglobin and myoglobin, widely used as reference systems for both computational and experimental method developments. Globins are able to bind (and perform reactions) with small ligands such as O 2 , NO, and CO, as well as other reactive oxygen and nitrogen species (RNOS), and given the extensive structural and spectroscopic available data in a wide variety of conformational and ligand bound states, such as the paradigmatic CO bound myoglobin, they have been extensively studied using QM/MM strategies. ,− …”

Section: Selected Examplesmentioning

confidence: 99%

Best Practices on QM/MM Simulations of Biological Systems

Clemente

Capece

Martí

2023

J. Chem. Inf. Model.

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During the second half of the 20th century, following structural biology hallmark works on DNA and proteins, biochemists shifted their questions from “what does this molecule look like?” to “how does this process work?”. Prompted by the theoretical and practical developments in computational chemistry, this led to the emergence of biomolecular simulations and, along with the 2013 Nobel Prize in Chemistry, to the development of hybrid QM/MM methods. QM/MM methods are necessary whenever the problem we want to address involves chemical reactivity and/or a change in the system’s electronic structure, with archetypal examples being the studies of an enzyme’s reaction mechanism and a metalloprotein’s active site. In the last decades QM/MM methods have seen an increasing adoption driven by their incorporation in widely used biomolecular simulation software. However, properly setting up a QM/MM simulation is not an easy task, and several issues need to be properly addressed to obtain meaningful results. In the present work, we describe both the theoretical concepts and practical issues that need to be considered when performing QM/MM simulations. We start with a brief historical perspective on the development of these methods and describe when and why QM/MM methods are mandatory. Then we show how to properly select and analyze the performance of the QM level of theory, the QM system size, and the position and type of the boundaries. We show the relevance of performing prior QM model system (or QM cluster) calculations in a vacuum and how to use the corresponding results to adequately calibrate those derived from QM/MM. We also discuss how to prepare the starting structure and how to select an adequate simulation strategy, including those based on geometry optimizations as well as free energy methods. In particular, we focus on the determination of free energy profiles using multiple steered molecular dynamics (MSMD) combined with Jarzynski’s equation. Finally, we describe the results for two illustrative and complementary examples: the reaction performed by chorismate mutase and the study of ligand binding to hemoglobins. Overall, we provide many practical recommendations (or shortcuts) together with important conceptualizations that we hope will encourage more and more researchers to incorporate QM/MM studies into their research projects.

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“…In the case of the heme systems the introduction of a QM/MM partition within the large p-system of the porphyrin ring has very little influence on the geometrical parameters. 42 The corrin ring of cobalamins is somehow similar to porphyrins. There are however some major differences: in corrins two of the four pyrrole units are directly connected.…”

Section: Importance Of the Qm/mm Partition Cobalaminsmentioning

confidence: 99%

Some critical issues in the application of quantum mechanics/molecular mechanics methods to the study of transition metal complexes

et al. 2003

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The application of quantum mechanics/molecular mechanics (QM/MM) methods in transition metal chemistry is growing steadily. It becomes therefore appropriate to assess the importance of a number of technical issues associated to their implementation. This work presents the discussion of several of these issues, including the eventual need for conformational searches, the choice of the MM force field and the possibility of its tuning. The examples presented here prove that a proper handling of these technical aspects can lead to an improvement in the efficiency and quality of QM/MM calculations.

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Theoretical modeling of the heme group with a hybrid QM/MM method

Cited by 35 publications

References 60 publications

Binding of dioxygen in a picket-fence porphyrin complex of iron. A theoretical QM/MM study

Binding of dioxygen in a picket-fence porphyrin complex of iron. A theoretical QM/MM study

Best Practices on QM/MM Simulations of Biological Systems

Some critical issues in the application of quantum mechanics/molecular mechanics methods to the study of transition metal complexes

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