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Development of constant-pH simulation methods in implicit solvent and applications in biomolecular systems

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Abstract

pH is a critical parameter for biological and technological systems directly related with electrical charges. It can give rise to peculiar electrostatic phenomena, which also makes them more challenging. Due to the quantum nature of the process, involving the forming and breaking of chemical bonds, quantum methods should ideally by employed. Nevertheless, due to the very large number of ionizable sites, different macromolecular conformations, salt conditions, and all other charged species, the CPU time cost simply becomes prohibitive for computer simulations, making this a quite complex problem. Simplified methods based on Monte Carlo sampling have been devised and will be reviewed here, highlighting the updated state-of-the-art of this field, advantages, and limitations of different theoretical protocols for biomolecular systems (proteins and nucleic acids). Following a historical perspective, the discussion will be associated with the applications to protein interactions with other proteins, polyelectrolytes, and nanoparticles.

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Acknowledgements

This work was supported in part by the Fundação de Amparo à Pesquisa do Estado de São Paulo [Fapesp 2015/16116-3 (FLBDS), Fapesp 2013/08166-5 and 2017/03204-7 (LGD)], the University Global Partnership Network (UGPN) Research Collaboration Fund (FLBDS) and the University College Dublin (UCD) through a visiting professors grant - Seed Funding (FLBDS). FLBDS also thanks the support of the University of São Paulo through the NAP-CatSinQ (Research Core in Catalysis and Chemical Synthesis), the computing hours at Rice University through the international collaboration program with USP and at The Swedish National Infrastructure for Computing (SNIC 2015/10-6), and the hospitality of the UCD School of Physics, UCD Institute for Discovery and CECAM/IRL. It is also a pleasure to acknowledge the collaboration in previous works and/or fruitful discussions with Bo Jönsson, Bo Svensson, Torbjörn Åkesson (in memoriam), Mikael Lund, Aatto Laaksonen, Erik Santiso, Samuela Pasquali, Philippe Derreumaux, Catherine Etchebest, and Donal MacKernan.

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  1. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Av. do café, s/no. – Universidade de São Paulo, BR-14040-903, Ribeirão Preto, SP, Brazil

    Fernando Luís Barroso daSilva

  2. UCD School of Physics, UCD Institute for Discovery, University College Dublin, Belfield, Dublin 4, Ireland

    Fernando Luís Barroso daSilva

  3. Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA

    Fernando Luís Barroso daSilva

  4. Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Av. Bandeirantes, 3900 – Universidade de São Paulo, BR-14040-901, Ribeirão Preto, SP, Brazil

    Luis Gustavo Dias

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  1. Fernando Luís Barroso daSilva
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  2. Luis Gustavo Dias
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Correspondence to Fernando Luís Barroso daSilva.

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Fernando Luís Barroso da Silva declares that he has no conflicts of interest. Luis Gustavo Dias declares that he has no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri.

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Barroso daSilva, F., Dias, L. Development of constant-pH simulation methods in implicit solvent and applications in biomolecular systems. Biophys Rev 9, 699–728 (2017). https://doi.org/10.1007/s12551-017-0311-5

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