Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing, PR China.
PLoS One. 2013 Apr 25;8(4):e62839. doi: 10.1371/journal.pone.0062839. Print 2013.
Natural products have been an important source of lead compounds for drug discovery. How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products.
We collected 19,7201 natural products structures, reported biological activities and virtual screening results. Principal component analysis was employed to explore the chemical space, and we found that there was a large portion of overlap between natural products and FDA-approved drugs in the chemical space, which indicated that natural products had large quantity of potential lead compounds. We also explored the network properties of natural product-target networks and found that polypharmacology was greatly enriched to those compounds with large degree and high betweenness centrality. In order to make up for a lack of experimental data, high throughput virtual screening was employed. All natural products were docked to 332 target proteins of FDA-approved drugs. The most potential natural products for drug discovery and their indications were predicted based on a docking score-weighted prediction model.
Analysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article. Natural products have vast chemical diversity, good drug-like properties and can interact with multiple cellular target proteins.
天然产物一直是药物发现的重要先导化合物来源。如何发现和评估具有生物活性的天然产物，对于从天然产物中获得药物/先导化合物至关重要。
我们收集了 197201 种天然产物结构、报道的生物活性和虚拟筛选结果。主成分分析被用于探索化学空间，我们发现天然产物和 FDA 批准药物在化学空间中有很大一部分重叠，这表明天然产物有大量潜在的先导化合物。我们还探索了天然产物-靶标网络的网络性质，发现那些具有大度数和高介数中心性的化合物有很大程度的多药性富集。为了弥补实验数据的不足，我们进行了高通量虚拟筛选。将所有天然产物对接至 332 种 FDA 批准药物的靶蛋白。基于对接评分加权预测模型，预测最有潜力用于药物发现的天然产物及其适应证。
本文对天然产物的分子描述符、化学空间分布和生物活性进行了分析。天然产物具有广泛的化学多样性、良好的类药性，并且可以与多个细胞靶标蛋白相互作用。
