Method for virtually screening cholesterol degrading medicine with 24-dehydrocholesterol reductase (DHCR24) being target point
A DHCR24, dehydrocholesterol technology, applied in special data processing applications, instruments, electrical digital data processing, etc., can solve the problems of high cost and less than 10% success rate, and achieve the effect of improving efficiency and shortening the research and development cycle.
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Embodiment 1
[0041] Example 1 A virtual screening method for cholesterol-lowering drugs targeting 24-dehydrocholesterol reductase
[0042] Proceed as follows:
[0043] (1) Establishment of the catalytic activity pocket of DHCR24 enzyme
[0044] 1. Download the amino acid sequence of DHCR24 protein on UniProt ( figure 1 ), and its three-dimensional structure was obtained by homology modeling. Predict protein structures on the I-TASSER Server online server. Using the scoring software LGscore (>1.5correct model) scoring result is 2.53, Maxsub (>0.1correct model) scoring result is 0.17, VERIFY3D (>80% of the residues had an averaged 3D-1D score>=0.2) scoring result is 82.79 %, the scoring result of Ramachandran plot (favoured and allowed region>90%) was 95%, and the structural model with higher scoring was finally determined as the three-dimensional structural model of DHCR24 protein ( figure 2 ).
[0045] 2. Pretreatment of the macromolecule receptor DHCR24. Process the higher-scoring ...
Embodiment 2
[0055] Example 2 Preliminary confirmation of the cholesterol-lowering efficacy of candidate drugs at the cellular level.
[0056] In order to further confirm the cholesterol-lowering efficacy of small molecule drug candidates obtained through virtual screening, two drugs, Conivaptan (DB00872) and Risperidone (DB00734), were verified at the cellular level. Firstly, hepG2 cells (human liver cancer cells) were cultured, and the optimal concentration of each drug was obtained according to the literature and experimental observations, and a complete medium (S+), a serum-free and antibiotic-free medium (S(-)), and a blank control group were set. , U18666a (known DHCR24 inhibitor, positive control group, the concentration is 2μM) and two drug groups (Conivaptan is 5μM, Risperidone is 1μM), 24 hours after administration, the cell pellet was collected to extract the total lipid, and the high-efficiency liquid phase determination. First use cholesterol (cholesterol) and cholesterol (de...
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