신종합성 마약류의 분자도킹을 통한 의존성 예측평가
Evaluation of Addictive Prediction through Molecular Docking of Designer Drugs
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본 연구에서는 임시마약류로 지정된 15종의 amphetamine (1-15)류 화합물들에 대해 molecular docking 기법을 사용하여 도파민 수송체에 대한 docking total score 값을 계산하고 이를 통해 수용체와의 binding affinity를 예측하였으며 화합물들간의 구조적 특성을 비교하였다. 그 결과, cathinone (3) 유도체 중 하나인 naphyrone (15)의 total score가 8.083으로 가장 높은 값을 보였다. 그리고 amphetamine 류 화합물들은 binding site의 아미노산 잔기사이에 Van der Waals 상호작용과 수소결합의 상호작용이강하게 일어남을 확인하였을 뿐 아니라, lipophilicity (ClogP)에 대하여 매우 높은 상관관계가 존재함을알았다. 이러한 결과는 다양하게 설계된 합성마약류들이 빠르게 확산될 수 있음을 시사하며 본 연구에서 수행한 in silico 기법이 신종 합성마약에 대한 생리활성평가법의 단점을 보완한 신종합성마약류 확산 방지를 위한 제도 마련의 근거가 되고자 한다.
Abstract
In this study, the docking total score for dopamine transporter was calculated by molecular docking technique using the 15 kinds of amphetamine compounds (1-15) designated as temporary drugs. From this, the binding affinity to the receptor was predicted and the structural characteristics of the compounds were compared. The total score of Naphyrone (15), one of the Cathinone (3) derivatives, was the highest at 8.083. Amphetamine compounds were found to be highly correlated with lipophilicity (ClogP) as well as confirming that the Van der Waals and the hydrogen bond interaction were strongly induced between the amino acid residues of the binding site. These results imply that various designer drugs can be rapidly diffused, and the in silico technique performed in this study is intended to be a basis for the establishment of a system to prevent the spread of new designer drugs, which complements the disadvantages of the method for evaluating physiological activity against new designer drugs.
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