Research Center for Drug Discovery, School of Pharmaceutical Sciences, and Institute of Human Virology, Sun Yat-Sen University, 132 East Circle at University City, Guangzhou, China.
J Pharm Pharm Sci. 2013;16(2):331-41. doi: 10.18433/j3c31s.
The Human Genome Project is producing a new biological 'periodic table', which defines all genes for making macromolecules (proteins, DNA, RNA, etc) and the relations between genes and their biological functions. We now need to consider whether to initiate a biochemome project aimed at discovering biochemistry's 'periodic table', which would define all molecular parts for making small molecules (natural products) and the relations between the parts and their functions to regulate genes. By understanding the Biochemome, we might be able to design biofunctional molecules based upon a set of molecular parts for drug innovation.
A number of algorithms for processing chemical structures are used to systematically derive chemoyls (natural building blocks) from a database of compounds identified in Traditional Chinese Medicine (TCM). The rules to combine chemoyls for biological activities are then deduced by mining an annotated TCM structure-activity database (ATCMD). Based upon the rules and the basic chemoyls, a chemical library can be biochemically profiled, virtual synthetic routes can be planned, and lead compounds can be identified for a specific drug target.
The Biochemome is the complete set of molecular components (chemoyls) in an organism and Biochemomics studies the rules governing their assembly and their evolution, together with the relations between the Biochemome and drug targets. This approach provides a new paradigm for drug discovery that is based on a comprehensive knowledge of the synthetic origins of biochemical diversity, and helps to direct biomimetic syntheses aimed at assembling quasi-natural product libraries for drug screening.
人类基因组计划正在产生一种新的生物“元素周期表”，它定义了所有制造大分子（蛋白质、DNA、RNA 等）的基因以及基因与其生物功能之间的关系。我们现在需要考虑是否启动一个旨在发现生物化学“元素周期表”的生物化学计划，该计划将定义所有制造小分子（天然产物）的分子部件以及这些部件与调节基因的功能之间的关系。通过了解生物化学，我们或许能够基于一套分子部件设计具有生物功能的分子，用于药物创新。
使用了一些用于处理化学结构的算法，从中药（TCM）中鉴定的化合物数据库中系统地推导化学元素（天然构建块）。然后通过挖掘注释中药结构-活性数据库（ATCMD）来推导出用于生物活性的化学元素组合规则。基于这些规则和基本的化学元素，可以对化学库进行生物化学分析，可以规划虚拟的合成路线，并为特定的药物靶点确定先导化合物。
生物化学是生物体中分子成分（化学元素）的完整集合，生物化学组学研究其组装和进化的规则，以及生物化学与药物靶点之间的关系。这种方法为药物发现提供了一种新的范例，它基于对生化多样性的合成起源的全面了解，并有助于指导旨在组装准天然产物库以进行药物筛选的仿生合成。
