biostudies-literatureUnknown12Solanki AMajor Histocompability Complex (MHC) Class I molecules allow cells to present foreign and endogenous peptides to T-Cells so that cells infected by pathogens can be identified and killed. Neural networks tools such as NetMHC-4.0 and NetMHCpan-4.1 are used to predict whether peptides will bind to variants of MHC molecules. These tools are trained on data gathered from binding affinity and eluted ligand experiments. However, these tools do not track hydrophobicity, a significant biochemical factor relevant to peptide binding, in their predictions. A previous study had concluded that the peptides predicted to bind to HLA-A*0201 by NetMHC-4.0 were much more hydrophobic than expected. This paper expands that study by also focusing on HLA-B*2705 and HLA-B*0801, which prefer binding hydrophilic anFrontiers in oncology1034810https://www.ebi.ac.uk/biostudies/studies/S-EPMC9677119biostudies-literatureHydrophobicity identifies false positives and false negatives in peptide-MHC binding.PMC9677119Riedel MSolanki ACornette JUdell JVasmatzis GfalseHydrophobicity identifies false positives and false negatives in peptide-MHC binding.Major Histocompability Complex (MHC) Class I molecules allow cells to present foreign and endogenous peptides to T-Cells so that cells infected by pathogens can be identified and killed. Neural networks tools such as NetMHC-4.0 and NetMHCpan-4.1 are used to predict whether peptides will bind to variants of MHC molecules. These tools are trained on data gathered from binding affinity and eluted ligand experiments. However, these tools do not track hydrophobicity, a significant biochemical factor relevant to peptide binding, in their predictions. A previous study had concluded that the peptides predicted to bind to HLA-A*0201 by NetMHC-4.0 were much more hydrophobic than expected. This paper expands that study by also focusing on HLA-B*2705 and HLA-B*0801, which prefer binding hydrophilic an2022-01-01T00:00:00Z20222025-04-05T10:57:52.674Z2025-04-05T10:57:52.674ZS-EPMC96771193641988810.3389/fonc.2022.1034810