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Natural selection based on coordination chemistry: computational assessment of [4Fe-4S]-maquettes with non-coded amino acids.

ABSTRACT: Cysteine is the only coded amino acid in biology that contains a thiol functional group. Deprotonated thiolate is essential for anchoring iron-sulfur ([Fe-S]) clusters, as prosthetic groups to the protein matrix. [Fe-S] metalloproteins and metalloenzymes are involved in biological electron transfer, radical chemistry, small molecule activation and signalling. These are key metabolic and regulatory processes that would likely have been present in the earliest organisms. In the context of emergence of life theories, the selection and evolution of the cysteine-specific R-CH₂-SH side chain is a fascinating question to confront. We undertook a computational [4Fe-4S]-maquette modelling approach to evaluate how side chain length can influence [Fe-S] cluster binding and stability in short 7-mer and long 16-mer peptides, which contained either thioglycine, cysteine or homocysteine. Force field-based molecular dynamics simulations for [4Fe-4S] cluster nest formation were supplemented with density functional theory calculations of a ligand-exchange reaction between a preassembled cluster and the peptide. Secondary structure analysis revealed that peptides with cysteine are found with greater frequency nested to bind preformed [4Fe-4S] clusters. Additionally, the presence of the single methylene group in cysteine ligands mitigates the steric bulk, maintains the H-bonding and dipole network, and provides covalent Fe-S(thiolate) bonds that together create the optimal electronic and geometric structural conditions for [4Fe-4S] cluster binding compared to thioglycine or homocysteine ligands. Our theoretical work forms an experimentally testable hypothesis of the natural selection of cysteine through coordination chemistry.

SUBMITTER: Szilagyi RK

PROVIDER: S-EPMC6802137 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Natural selection based on coordination chemistry: computational assessment of [4Fe-4S]-maquettes with non-coded amino acids.

Szilagyi Robert K RK Hanscam Rebecca R Shepard Eric M EM McGlynn Shawn E SE

Interface focus 20191018 6

Cysteine is the only coded amino acid in biology that contains a thiol functional group. Deprotonated thiolate is essential for anchoring iron-sulfur ([Fe-S]) clusters, as prosthetic groups to the protein matrix. [Fe-S] metalloproteins and metalloenzymes are involved in biological electron transfer, radical chemistry, small molecule activation and signalling. These are key metabolic and regulatory processes that would likely have been present in the earliest organisms. In the context of emergenc ...[more]

PMID: 31641437

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Project description:Design problems of finding efficient patterns, adaptation of complex molecules to external environments, affinity of molecules to specific targets, dynamic adaptive behavior of chemical systems, reconstruction of 3D structures from diffraction data are examples of difficult to solve optimal design or inverse search problems. Nature inspires evolution strategies to solve design problems that are based on selection of successful adaptations and heritable traits over generations. To exploit this strategy in the creation of new materials, a concept of adaptive chemistry was proposed to provide a route for synthesis of self-adapting molecules that can fit to their environment. We propose a computational method of an efficient exhaustive search exploiting massive parallelization on modern GPUs, which finds a solution for an inverse problem by solving repetitively a direct problem in the mean field approximation. One example is the search for a composition of a copolymer that allows the polymer to translocate through a lipid membrane at a minimal time. Another example is a search of a copolymer sequence that maximizes the polymer load in the micelle defined by the radial core-shell potentials. The length and the composition of the sequence are adjusted to fit into the restricted environment. Hydrogen bonding is another pathway of adaptation to the environment through reversible links. A linear polymer that interacts with water through hydrogen bonds adjusts the position of hydrogen bonds along the chain as a function of the concentration field around monomers. In the last example, branching of the molecules is adjusted to external fields, providing molecules with annealed topology, that can be flexibly changed by changing external conditions. The method can be generalized and applied to a broad spectrum of design problems in chemistry and physics, where adaptive behavior in multi-parameter space in response to environmental conditions lead to non-trivial patterns or molecule architectures and compositions. It can further be combined with machine learning or other optimization techniques to explore more efficiently the parameter space.

Project description:The all-ferrous, carbene-capped Fe(4)S(4) cluster, synthesized by Deng and Holm (DH complex), has been studied with density functional theory (DFT). The geometry of the complex was optimized for several electronic configurations. The lowest energy was obtained for the broken-symmetry (BS) configuration derived from the ferromagnetic state by reversing the spin projection of one of the high spin (S(i) = 2) irons. The optimized geometry of the latter configuration contains one unique and three equivalent iron sites, which are both structurally and electronically clearly distinguishable. For example, a distinctive feature of the unique iron site is the diagonal Fe···S distance, which is 0.3 Å longer than for the equivalent irons. The calculated (57)Fe hyperfine parameters show the same 1:3 pattern as observed in the Mössbauer spectra and are in good agreement with experiment. BS analysis of the exchange interactions in the optimized geometry for the 1:3, M(S) = 4, BS configuration confirms the prediction of an earlier study that the unique site is coupled to the three equivalent ones by strong antiferromagnetic exchange (J > 0 in J ?(j<4)?(4)·?(j)) and that the latter are mutually coupled by ferromagnetic exchange (J' < 0 in J' ?(i<j<4)?(i)·?(j)). In combination, these exchange couplings stabilize an S = 4 ground state in which the composite spin of the three equivalent sites (S(123) = 6) is antiparallel to the spin (S(4) = 2) of the unique site. Thus, DFT analysis supports the idea that the unprecedented high value of the spin of the DH complex and, by analogy, of the all-ferrous cluster of the Fe-protein of nitrogenase, results from a remarkably strong dependence of the exchange interactions on cluster core geometry. The structure dependence of the exchange-coupling constants in the Fe(II)-(?(3)-S)(2)-Fe(II) moieties of the all-ferrous clusters is compared with the magneto-structural correlations observed in the data for dinuclear copper complexes. Finally, we discuss two all-ferric clusters in the light of the results for the all-ferrous cluster.

Dataset Information

Natural selection based on coordination chemistry: computational assessment of [4Fe-4S]-maquettes with non-coded amino acids.

Publications

Natural selection based on coordination chemistry: computational assessment of [4Fe-4S]-maquettes with non-coded amino acids.

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