Modeling Peptide–Protein Interactions by a Logo-Based Method: Application in Peptide–HLA Binding Predictions

Molecules, vol. 29, pp. 284

Abstract

Peptide-protein interactions form a cornerstone in molecular biology, governing cellular signaling, structure, and enzymatic activities in living organisms. Improving computational models and experimental techniques to describe and predict these interactions remains an ongoing area of research. Here, we present a computational method for peptide-protein interactions' description and prediction based on leveraged amino acid frequencies within specific binding cores. Utilizing normalized frequencies, we construct quantitative matrices (QMs), termed 'logo models' derived from sequence logos. The method was developed to predict peptide binding to HLA-DQ2.5 and HLA-DQ8.1 proteins associated with susceptibility to celiac disease. The models were validated by more than 17,000 peptides demonstrating their efficacy in discriminating between binding and non-binding peptides. The logo method could be applied to diverse peptide-protein interactions, offering a versatile tool for predictive analysis in molecular binding studies.

Authors 6

1. Irini Atanas Doytchinova corresponding

   Medical University of Sofia

   Affiliation as printed

   Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria

2. Mariyana Atanasova

   Medical University of Sofia

   Affiliation as printed

   Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria

3. Antonio Fernandez

   European Food Safety Authority

   Affiliation as printed

   European Food Safety Authority, 43126 Parma, Italy

4. Francisco Javier Moreno

   Consejo Superior de Investigaciones Científicas · Instituto de Investigación en Ciencias de la Alimentación

   Affiliation as printed

   Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM, CEI (UAM+CSIC), Nicolás Cabrera, 9, 28049 Madrid, Spain

5. Frits Koning Aachen Department of Immunohematology and Blood Transfusion

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands

6. Ivan Dimitrov

   Medical University of Sofia

   Affiliation as printed

   Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria