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Using Structural and Physical–Chemical Parameters to Identify, Classify, and Predict Functional Districts in Proteins—The Role of Electrostatic Potential

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Computational Electrostatics for Biological Applications

Abstract

In this chapter, we will overview the role of the local protein structure environment (which we will call here: nano-environment) in maintaining the functional purpose of different protein districts (defined as protein structure sites delimited by their functional objectives). Namely, we suggest that the local environment at each protein point and/or region reflects, not only its constitutional/structural role, but also its contribution to providing necessary and required characteristics for the functional objective that such particular site is supposed to have. For instance, protein–protein communication is executed through protein interfaces, and amino acid residues belonging to that site must have some specific characteristics which do not only differentiate them from the free surface residues, but also make possible that two very specific proteins may engage, bind and by doing so, perform their function. Similarly, enzyme function is normally related to activity of its catalytic site residues (CSRs). Obviously, these very peculiar residues are embedded in a very specific nano-environment (defined also by the contribution of CSR). Consequently, the enzyme function could be described in terms of characteristics of the CSRs and their surroundings. Based on the above considerations, and assuming that the local nano-environment is not only defining the protein district function, but it is also a concept for which we can design specific metrics to quantify it, and a specific set of properties to describe it, we studied the role of different descriptors and found that, together with hydrophobicity, electrostatic potential is of fundamental importance. As we will better detail in the course of this work, the electrostatic potential might not always be the top ranked property defining the nano-environment of interest, but it is, however, always present, contributing significantly in carving proper protein district characteristics for specific structure/function purposes.

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Authors and Affiliations

  1. Embrapa Agricultural Informatics, Campinas, Brazil

    Goran Neshich, Inacio Henrique Yano, Ivan Mazoni & Jose Gilberto Jardine

  2. Unicamp, Campinas, Brazil

    Izabella Agostinho Pena Neshich, Jose Augusto Salim & Luiz Borro

  3. UNESP, Sao Jose do Rio Preto, Brazil

    Fabio Moraes

  4. CONCEPT Lab—CompuNet, Istituto Italiano di Tecnologia, Genova, Italy

    Walter Rocchia

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  1. Goran Neshich
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Correspondence to Goran Neshich .

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  1. CONCEPT Lab - CompuNet, Istituto Italiano di Tecnologia, Genova, Italy

    Walter Rocchia

  2. Institute of Applied Mathematics and Inf, National Research Council, Genova, Italy

    Michela Spagnuolo

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Neshich, G. et al. (2015). Using Structural and Physical–Chemical Parameters to Identify, Classify, and Predict Functional Districts in Proteins—The Role of Electrostatic Potential. In: Rocchia, W., Spagnuolo, M. (eds) Computational Electrostatics for Biological Applications. Springer, Cham. https://doi.org/10.1007/978-3-319-12211-3_12

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