Pfizer Inc., 35 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA.
J Chem Inf Model. 2012 Oct 22;52(10):2796-806. doi: 10.1021/ci3001925. Epub 2012 Sep 26.
When biological macromolecules are used as therapeutic agents, it is often necessary to introduce non-natural chemical modifications to improve their pharmaceutical properties. The final products are complex structures where entities such as proteins, peptides, oligonucleotides, and small molecule drugs may be covalently linked to each other, or may include chemically modified biological moieties. An accurate in silico representation of these complex structures is essential, as it forms the basis for their electronic registration, storage, analysis, and visualization. The size of these molecules (henceforth referred to as "biomolecules") often makes them too unwieldy and impractical to represent at the atomic level, while the presence of non-natural chemical modifications makes it impossible to represent them by sequence alone. Here we describe the Hierarchical Editing Language for Macromolecules ("HELM") and demonstrate its utility in the representation of structures such as antisense oligonucleotides, short interference RNAs, peptides, proteins, and antibody drug conjugates.
当生物大分子被用作治疗剂时，通常需要引入非天然的化学修饰来改善它们的药物性质。最终产物是复杂的结构，其中蛋白质、肽、寡核苷酸和小分子药物等实体可能彼此共价连接，或者可能包含化学修饰的生物部分。这些复杂结构的准确的计算模型表示是必不可少的，因为它是它们的电子注册、存储、分析和可视化的基础。这些分子的大小（此后称为“生物分子”）通常使得它们在原子水平上过于笨拙和不切实际，而非天然化学修饰的存在使得仅通过序列表示它们变得不可能。在这里，我们描述了大分子的分层编辑语言（“HELM”），并演示了它在反义寡核苷酸、短干扰 RNA、肽、蛋白质和抗体药物偶联物等结构表示中的用途。
