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. 2022 Oct 8;121(22):4342–4357. doi: 10.1016/j.bpj.2022.10.008

Table 2.

Binding properties for eight candidate peptides calculated from all-atom MD simulations

Peptide Stable binding duration (ns) Binding free energy (kcal/mol) SEM Protein-peptide interaction energy (kcal/mol) Desolvation energy (kcal/mol) Sequence No. of stable peptide-protein hydrogen bonds
Y36_cls3_M2_M4_R8 278 −25.9 0.06 −85.6 59.7 ACE-AMAMGYPRASY-NH2 0
Y36_cls3_R2_M4 394 −46.2 0.06 −140.4 94.2 ACE-ARAMGYPGASY-NH2 2 Peptide 1
Y36_cls5_M2_R4_W8_Y9 184 −22.3 0.08 −64.1 41.8 ACE-AMARGYPWYSY-NH2 0
Y36_cls5_R2_F4_I8_Y9 500 −42.3 0.06 −124.5 82.2 ACE-ARAFGYPIYSY-NH2 1 Peptide 2
Y45_cls1_M3_R4_M8_I10 172 −16.2 0.06 −66.2 50 ACE-SYMRAYPMQIP-NH2 0
Y45_cls1_M3_R4_M8_M10 91 −35.5 0.2 −87.8 52.3 ACE-SYMRAYPMQMP-NH2 0
Y45_cls70_Y1_M8_R9_F10_R11 500 −34.4 0.5 −136.6 102.2 ACE-YYPGAYPMRFR-NH2 0
Y45_cls70_Y1_R8_R9_Y10_R11 500 −29.5 0.04 −169.3 139.8 ACE-YYPGAYPRRYR-NH2 2 Peptide 3

These peptides are the best binders according to their duration of binding to the CTD, number of protein-peptide hydrogen bonds, and binding free energy. These peptides were selected for experimental testing and were designated as peptides 1, 2, and 3 in the experimental assays. The last row shows peptide 3, which was found to be a positive hit in the agglutination assay.