Parallel Computation of Conformational Stability for CD4+ T-cell Epitope Prediction

Avik Bhattacharya, James O. Wrabl, Samuel J. Landry, Ramgopal R. Mettu

Abstract: Antigen-presenting cells present peptides derived from foreign pathogens in the form of peptide-MHCII complexes to induce immune response. Two important and interrelated processes that lead to peptide presentation are antigen processing and peptide-MHCII binding. Although the latter phenomenon has been thoroughly studied and incorporated into CD4+ T cell epitope prediction tools, antigen processing has remained under-explored as a means to improve epitope prediction tools. In prior work, our group developed the antigen processing likelihood (APL) metric [1] and showed that it can be used to effectively predict CD4+ T-cell epitopes either alone or in combination with peptide-MHCII binding affinity-based tools. A key component of the APL scoring approach is a residue-wise conformational stability metric known as COREX [2], which estimates the likelihood of unfolding at each residue using a free energy approximation. COREX calculation takes a significant amount of time (6-8 hours) and thus limits our ability to rapidly predict CD4+ T-cell epitopes over large antigen sets. In this paper, we give a parallel algorithm to compute the COREX metric and demonstrate its utility over several benchmarks. We achieve a 196-fold speedup with our parallel algorithm, bringing the overall computation of APL down from hours to minutes.