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TI2BioP: Topological Indices to BioPolymers. Its practical use to unravel cryptic bacteriocin-like domains

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Abstract

Bacteriocins are proteinaceous toxins produced and exported by both gram-negative and gram-positive bacteria as a defense mechanism. The bacteriocin protein family is highly diverse, which complicates the identification of bacteriocin-like sequences using alignment approaches. The use of topological indices (TIs) irrespective of sequence similarity can be a promising alternative to predict proteinaceous bacteriocins. Thus, we present Topological Indices to BioPolymers (TI2BioP) as an alignment-free approach inspired in both the Topological Substructural Molecular Design (TOPS-MODE) and Markov Chain Invariants for Network Selection and Design (MARCH-INSIDE) methodology. TI2BioP allows the calculation of the spectral moments as simple TIs to seek quantitative sequence-function relationships (QSFR) models. Since hydrophobicity and basicity are major criteria for the bactericide activity of bacteriocins, the spectral moments (HPμ k ) were derived for the first time from protein artificial secondary structures based on amino acid clustering into a Cartesian system of hydrophobicity and polarity. Several orders of HPμ k characterized numerically 196 bacteriocin-like sequences and a control group made up of 200 representative CATH domains. Subsequently, they were used to develop an alignment-free QSFR model allowing a 76.92% discrimination of bacteriocin proteins from other domains, a relevant result considering the high sequence diversity among the members of both groups. The model showed a prediction overall performance of 72.16%, detecting specifically 66.7% of proteinaceous bacteriocins whereas the InterProScan retrieved just 60.2%. As a practical validation, the model also predicted successfully the cryptic bactericide function of the Cry 1Ab C-terminal domain from Bacillus thuringiensis’s endotoxin, which has not been detected by classical alignment methods.

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Acknowledgments

The authors acknowledge the Portuguese Fundação para a Ciência e a Tecnologia (FCT) for financial support to GACH (SFRH/BD/47256/2008), AMH (SFRH/BPD/63946/2009) and the project PTDC/BIA-BDE/69144/2006 and PTDC/AAC-AMB/104983/2008. GACH acknowledges the Assistant Professor Roberto I. Vázquez-Padrón from the University of Miami, USA for providing useful information on the Cry 1Ab endotoxin from Bt subsp. kurstaki.

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Authors and Affiliations

  1. CIMAR/CIIMAR, Centro Interdisciplinar de Investigação Marinha e Ambiental, Universidade do Porto, Rua dos Bragas, 177, 4050-123, Porto, Portugal

    Guillermín Agüero-Chapin, Vítor Vasconcelos & Agostinho Antunes

  2. Molecular Simulation and Drug Design (CBQ), Central University of Las Villas, 54830, Santa Clara, Cuba

    Guillermín Agüero-Chapin, Gisselle Pérez-Machado, Reinaldo Molina-Ruiz, Yunierkis Pérez-Castillo & Aliuska Morales-Helguera

  3. Department of Organic Chemistry, Vigo University, 36200, Vigo, Spain

    Yunierkis Pérez-Castillo

  4. Department of Chemistry, Central University of Las Villas, Santa Clara, 54830, Villa Clara, Cuba

    Aliuska Morales-Helguera

  5. REQUIMTE, Department of Chemistry, University of Porto, 4169-007, Porto, Portugal

    Aliuska Morales-Helguera

  6. Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal

    Guillermín Agüero-Chapin & Vítor Vasconcelos

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  1. Guillermín Agüero-Chapin
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  2. Gisselle Pérez-Machado
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  3. Reinaldo Molina-Ruiz
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  6. Vítor Vasconcelos
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  7. Agostinho Antunes
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Correspondence to Agostinho Antunes.

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Agüero-Chapin, G., Pérez-Machado, G., Molina-Ruiz, R. et al. TI2BioP: Topological Indices to BioPolymers. Its practical use to unravel cryptic bacteriocin-like domains. Amino Acids 40, 431–442 (2011). https://doi.org/10.1007/s00726-010-0653-9

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