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Quantum mechanical treatment of As3+-thiol model compounds: implication for the core structure of As(III)-metallothionein

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Abstract

Exposure to inorganic arsenic (As) is one of the major health concerns in several regions around the world. Binding of As(III) with thiols is central to the mechanisms related to its toxicity, detoxification, and therapeutic effects. Due to its high thiol content, metallothionein (MT) is presumed to play an important role in case of arsenic toxicity. Consequences of these As-thiol interactions are not yet clear due to various difficulties in the characterization of arsenic bound proteins by spectroscopic techniques. Computational modeling can be a reliable approach in predicting the molecular structures of such complexes. This paper presents the results of a systematic study on different As(III)-thiol model compounds conducted by both ab initio and DFT methods with different Gaussian type basis sets. Proficiency of these theoretical methods has been evaluated in terms of bond lengths, bond angles, free energy, partial atomic charges, computational cost, and comparison with the experimental data. It has been demonstrated that the DFT-B3LYP/6-311+G(3df) functional offers better accuracy in predicting the structure and the UV absorption spectra of As(III)-thiol complexes. The results of the present study also helps in defining the boundaries for the core of arsenic bound MT so that quantum mechanical/molecular mechanical (QM/MM) methods can be employed to predict the structural and functional aspects of the protein.

Optimized structural parameters of As3+-thiol model compounds

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Acknowledgements

This work is funded by University Grant Commission (UGC), New Delhi, India vide grant no. F. No. 37-317/2009 (SR). Department of Science and Technology, New Delhi, India is gratefully acknowledged for providing the workstation facility at Department of Biophysics, Panjab University, Chandigarh under the DST-FIST grant. R.G. is thankful to UGC for providing financial assistance in the form of Junior/Senior Research Fellowship. B.P.M. thankfully acknowledges the financial assistance provided by Indian Council Medical Research, India in the form of Research Associateship.

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  1. Department of Biophysics, Panjab University, Chandigarh, India, 160014

    Roobee Garla, Narinder Kaur, Mohinder Pal Bansal, Mohan Lal Garg & Biraja Prasad Mohanty

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  1. Roobee Garla
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  2. Narinder Kaur
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  3. Mohinder Pal Bansal
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Correspondence to Biraja Prasad Mohanty.

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Garla, R., Kaur, N., Bansal, M.P. et al. Quantum mechanical treatment of As3+-thiol model compounds: implication for the core structure of As(III)-metallothionein. J Mol Model 23, 78 (2017). https://doi.org/10.1007/s00894-017-3247-6

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  • DOI: https://doi.org/10.1007/s00894-017-3247-6

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