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基于分子对接技术及CoMSIA/HQSAR辅助的二羟基多氯联苯衍生物分子修饰 被引量:5
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作者 辛美玲 褚振华 李鱼 《高等学校化学学报》 SCIE EI CAS CSCD 北大核心 2018年第2期299-309,共11页
利用类二噁英类多氯联苯(PCBs)大气氧化降解产物二羟基多氯联苯与2,3-二羟基联苯双加氧酶(Bphc,PDB ID:1KW6)进行分子对接,构建以分子结构参数为自变量,对接打分函数(K_d,代表对接活性)为因变量的分子相似性指数分析(Co MSIA)与分子全... 利用类二噁英类多氯联苯(PCBs)大气氧化降解产物二羟基多氯联苯与2,3-二羟基联苯双加氧酶(Bphc,PDB ID:1KW6)进行分子对接,构建以分子结构参数为自变量,对接打分函数(K_d,代表对接活性)为因变量的分子相似性指数分析(Co MSIA)与分子全息定量结构-活性相关关系(HQSAR)模型,并对二羟基多氯联苯进行分子修饰,研究结果表明,Bphc酶对二羟基多氯联苯均有不同程度的降解能力,影响Bphc酶对接活性的氨基酸残基为His145,Val147,Ile174,His194,His208,His209,His240,Asn242,Tyr249及Thr280,且二羟基多氯联苯与氨基酸残基对接形成的氢键越多对接活性越高.建立了CoMSIA和HQSAR模型耦合的二羟基多氯联苯分子取代活性精确定位方法,以打分函数较低的二羟基多氯联苯5,6-2OH-CB60为目标分子,设计出8种打分函数显著提升的新型分子,其对接活性提高65%~185%,分子毒性(IC_(50))下降10%~83%,生物富集性(BCF)下降4%~27%,迁移性(K_(OA))与半衰期(t_(1/2))增降幅基本不变.所设计新型分子反应路径的推断可以验证二羟基多氯联苯5,6-2OH-CB60在环境中与活性自由基或与活性分子反应生成所设计的新型5,6-2OH-CB60分子,即类二噁英类PCBs可通过大气氧化降解最终生成酶降解性显著提高的新型二羟基多氯联苯,达到进一步控制类二噁英类PCBs环境行为的目的. 展开更多
关键词 类二噁英类多氯联苯 二羟基多氯联苯 bphc 分子对接 分子相似性指数分数 分子全息定量结构-活性相关关系
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What Is the Best Surgical Approach for Bilateral Pulmonary Hydatid Cysts in Children?
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作者 Aram Baram 《World Journal of Cardiovascular Surgery》 2015年第3期30-38,共9页
Introduction: The most common site for hydatid cysts in children is the lungs while in adult hepatic cysts are predominant. Bilateral pulmonary involvement is relatively rare and its surgical management is poorly desc... Introduction: The most common site for hydatid cysts in children is the lungs while in adult hepatic cysts are predominant. Bilateral pulmonary involvement is relatively rare and its surgical management is poorly described in the current literature. Until now no definite consensus has been described in the literature for the ideal surgical approach in pediatric bilateral pulmonary hydatid cysts (BPHC). The aim of this prospective cohort study was to describe the problems encountered in treating pediatric BPHC by two different surgical techniques. Patients and Methods: Between June 2007 and June 2014, 60 children (group one = 31, group two = 29) with BPHC were operated on in our center. Group one included all children with BPHC operated by single session bilateral anterolateral mini-thoracotomy. Group two included all cases operated by two stage standard posterolateral thoracotomy at 21 days interval. Results: In group one (19 males and 12 females), the mean age was 8.9 years (3.5-17). In group two, there were 29 cases (18 males and 11 females), the mean age was 9.6 years (2-17). There was no significant statistical difference in terms of the presentations and age distribution. The duration of surgery in group one was significantly shorter and the duration of hospital stay was significantly shorter as well (group one 3.6 days versus 4.6 days in the second group). Pain scale was not more in the first group as it was believed to be. Conclusion: We believe that single session bilateral anterolateral thoracotomy is a better approach than either one stage successive thoracotomies, median sternotomy or clamshell thoracotomy as it involves less postoperative pain and does not precipitate a decrease in the respiratory capacity. 展开更多
关键词 BILATERAL PULMONARY HYDATID CYST (bphc) BILATERAL ANTEROLATERAL THORACOTOMY
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