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Computational Approaches: An Underutilized Tool in the Quest to Elucidate Radical SAM Dynamics.

ABSTRACT: Enzymes are biological catalysts whose dynamics enable their reactivity. Visualizing conformational changes, in particular, is technically challenging, and little is known about these crucial atomic motions. This is especially problematic for understanding the functional diversity associated with the radical S-adenosyl-L-methionine (SAM) superfamily whose members share a common radical mechanism but ultimately catalyze a broad range of challenging reactions. Computational chemistry approaches provide a readily accessible alternative to exploring the time-resolved behavior of these enzymes that is not limited by experimental logistics. Here, we review the application of molecular docking, molecular dynamics, and density functional theory, as well as hybrid quantum mechanics/molecular mechanics methods to the study of these enzymes, with a focus on understanding the mechanistic dynamics associated with turnover.

SUBMITTER: Blue TC

PROVIDER: S-EPMC8124187 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Computational Approaches: An Underutilized Tool in the Quest to Elucidate Radical SAM Dynamics.

Blue Tamra C TC Davis Katherine M KM

Molecules (Basel, Switzerland) 20210429 9

Enzymes are biological catalysts whose dynamics enable their reactivity. Visualizing conformational changes, in particular, is technically challenging, and little is known about these crucial atomic motions. This is especially problematic for understanding the functional diversity associated with the radical <i>S</i>-adenosyl-L-methionine (SAM) superfamily whose members share a common radical mechanism but ultimately catalyze a broad range of challenging reactions. Computational chemistry approa ...[more]

PMID: 33946806

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