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基于分子对接技术对维生素D3羟化酶底物谱的筛选及验证
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Abstract:
维生素D3羟化酶(Vdh)是生物法合成维生素D3 (VD3)活性形式25(OH)VD3和1α,25(OH)2VD3的关键酶之一。然而，至今对Vdh的天然底物了解甚少，限制了其工业上的应用。为了提高Vdh的商业价值，找到Vdh的最佳底物，探究Vdh与底物的作用机制，深入挖掘Vdh的应用潜力。本研究以VD3与Vdh的结合模型为基础，利用Autodock分子对接技术对ZINC化合物数据库进行筛选，结合打分，性质筛选以及广义伯恩表面积法(MM/GBSA)计算结合自由能，最终从中挑选出4个小分子进行了实验验证。实验结果与筛选结果一致，4个小分子均能与Vdh发生反应，范德华力是Vdh与小分子结合的主要驱动力，推测Vdh是生产类固醇类药物的潜在生物催化剂。我们的研究为生物合成类固醇药物提供了新思路，也为深入了解Vdh提供了理论基础。
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