Abstract：
B-cell epitope prediction is key to developing peptide-based vaccines and immunodiagnostics along with antibodies for prophylactic, therapeutic and/or diagnostic use. This entails estimating paratope binding affinity for variable-length peptidic sequences subject to constraints on both paratope accessibility and antigen conformational flexibility, as described herein for the HAPTIC2/HEPTAD User Toolkit (HUT). HUT comprises the Heuristic Affinity Prediction Tool for Immune Complexes 2 (HAPTIC2), the HAPTIC2-like Epitope Prediction Tool for Antigen with Disulfide (HEPTAD) and the HAPTIC2/HEPTAD Input Preprocessor (HIP). HIP enables tagging of residues (e.g., in hydrophobic blobs, ordered regions and glycosylation motifs) for exclusion from downstream analyses by HAPTIC2 and HEPTAD. HAPTIC2 estimates paratope binding affinity for disulfide-free disordered peptidic antigens (by analogy between flexible-ligand docking and protein folding), from terms attributed to compaction (in view of sequence length, charge and temperature-dependent polyproline-II helical propensity), collapse (disfavored by residue bulkiness) and contact (with glycine and proline regarded as polar residues that hydrogen bond with paratopes). HEPTAD analyzes antigen sequences that each contain two cysteine residues for which the impact of disulfide pairing is estimated as a correction to the free-energy penalty of compaction. All of HUT is freely accessible online ( https://freeshell.de/~badong/hut.htm ).
摘要：
B细胞表位预测是开发基于肽的疫苗和免疫诊断方法以及用于预防的抗体的关键。治疗和/或诊断用途。这需要估计可变长度肽序列的互补位结合亲和力，同时受到互补位可接近性和抗原构象灵活性的限制。如本文针对HAPTIC2/HEPTAD用户工具包(HUT)所述。HUT包含免疫复合物2的启发式亲和力预测工具（HAPTIC2），含二硫化物抗原的HAPTIC2样抗原表位预测工具(HEPTAD)和HAPTIC2/HEPTAD输入预处理器(HIP)。HIP能够标记残基(例如，在疏水斑点中，有序区域和糖基化基序），用于从HAPTIC2和HEPTAD的下游分析中排除。HAPTIC2估计对无二硫键无序肽抗原的互补位结合亲和力（通过柔性配体对接和蛋白质折叠之间的类比），从归因于压缩的术语(鉴于序列长度，电荷和温度依赖性聚脯氨酸-II螺旋倾向)，塌陷（由于残基庞大而不受欢迎）和接触（甘氨酸和脯氨酸被视为与互补体氢键的极性残基）。HEPTAD分析各自含有两个半胱氨酸残基的抗原序列,其中二硫键配对的影响被估计为对压缩的自由能损失的校正。所有HUT都可以免费在线访问（https://freeshell。德/~巴东/小屋。htm).
