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Illuminating the “Twilight Zone”: Advances in Difficult Protein Modeling

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Homology Modeling

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2627))

Abstract

Homology modeling was long considered a method of choice in tertiary protein structure prediction. However, it used to provide models of acceptable quality only when templates with appreciable sequence identity with a target could be found. The threshold value was long assumed to be around 20–30%. Below this level, obtained sequence identity was getting dangerously close to values that can be obtained by chance, after aligning any random, unrelated sequences. In these cases, other approaches, including ab initio folding simulations or fragment assembly, were usually employed. The most recent editions of the CASP and CAMEO community-wide modeling methods assessment have brought some surprising outcomes, proving that much more clues can be inferred from protein sequence analyses than previously thought. In this chapter, we focus on recent advances in the field of difficult protein modeling, pushing the threshold deep into the “twilight zone”, with particular attention devoted to improvements in applications of machine learning and model evaluation.

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Acknowledgments

The research was partially performed under OPUS grant from National Science Center (NCN, Poland), grant number UMO-2017/27/B/NZ7/01767 (to A.A.K).

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Authors and Affiliations

  1. Department of Synthesis and Chemical Technology of Pharmaceutical Substances with Computer Modelling Laboratory, Medical University of Lublin, Lublin, Poland

    Damian Bartuzi, Agnieszka A. Kaczor & Dariusz Matosiuk

  2. University of Eastern Finland, School of Pharmacy, Kuopio, Finland

    Agnieszka A. Kaczor

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  1. Damian Bartuzi
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  2. Agnieszka A. Kaczor
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  3. Dariusz Matosiuk
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Correspondence to Damian Bartuzi .

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  1. Faculty of Chemistry, University of Warsaw, Warsaw, Poland

    Sławomir Filipek

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Bartuzi, D., Kaczor, A.A., Matosiuk, D. (2023). Illuminating the “Twilight Zone”: Advances in Difficult Protein Modeling. In: Filipek, S. (eds) Homology Modeling. Methods in Molecular Biology, vol 2627. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2974-1_2

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  • DOI: https://doi.org/10.1007/978-1-0716-2974-1_2

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