دراسات النمذجة الجزيئية لبعض النباتات النباتية من جزء Ficus sycomorus كمثبطات محتملة لإنزيم السيتوكروم CYP6P3 من Anopheles coluzzi

المؤلفون

  • Abba Babandi جامعة بايرو، نيجيريا
  • Chioma A. Anosike جامعة نيجيريا، نيجيريا
  • Lawrence U.S. Ezeanyika جامعة نيجيريا، نيجيريا
  • Kemal Yelekçi جامعة قادر هاس، تركيا
  • Abdullahi Ibrahim Uba مركز بكين لبحوث العلوم الحاسوبية، الصين

DOI:

https://doi.org/10.35516/jjps.v15i2.324

الكلمات المفتاحية:

نمذجة التنادد، الالتحام الجزيئي كفاءة يجند محاكاة الديناميات الجزيئية، مثبطات CYP6P3

الملخص

العقبة الرئيسية في مكافحة الملاريا هي مقاومة البعوض للمبيدات الحشرية، بما في ذلك البيرثرويد. ترجع المقاومة بشكل أساسي إلى الإفراط في التعبير عن إنزيمات إزالة السموم مثل السيتوكرومات. يمكن تقليل تحمل المبيدات الحشرية عن طريق مثبطات P450s المشاركة في إزالة السموم من المبيدات الحشرية. هنا، لتصميم مثبطات CYP6P3 المحتملة، تم إنشاء نموذج تماثل للإنزيم باستخدام التركيب البلوري للبكتيريا الزرقاء المرتبط بحمض الريتينويك CYP120A1 (معرف PDB: 2VE3 ؛ القرار: 2.1 Å). تم استخدام دراسة الالتحام الجزيئي والنمذجة الحسابية لتحديد الإمكانات المثبطة لبعض النباتات النباتية المعزولة من Ficus sycomorus ضد Anopheles coluzzii النموذجي P450 ، CYP6P3 ، المتورط في المقاومة. تم تحليل خصائص تحسين الترابط المحتمل (LE) باستخدام النماذج الرياضية القياسية. المركبات 5 و 8 و 9 مرتبطة بحديد Heme لـ CYP6P3 ضمن 3.14 و 2.47 و 2.59 Å، على التوالي. قدرت طاقات الارتباط الخاصة بكل منها بـ -8.93 و -10.44 و -12.56 كيلو كالوري / مول. لفحص ثبات وضع الربط الخاص بهم، تم إخضاع مجمعات الالتحام الناتجة من هذه المركبات باستخدام CYP6P3 لمحاكاة 50 نانوثانية MD. ظلت المركبات مرتبطة بالإنزيم و Fe (Heme): يبدو أن مسافة O (Ligand) قد تم الحفاظ عليها بمرور الوقت. يؤدي التنسيق بين ليجند قوي إلى حديد الهيم إلى تحويل الحديد من الشكل العالي إلى شكل الدوران المنخفض المستقر ومنع الأكسجين من الارتباط بالهيم وبالتالي تثبيط النشاط التحفيزي. أظهر مؤشر LE القدرة العالية لهذه المركبات (5 و 8) لتوفير جزء أساسي لتحسين مثبطات P450 القوية.

السير الشخصية للمؤلفين

Abba Babandi، جامعة بايرو، نيجيريا

1 قسم الكيمياء الحيوية، جامعة بايرو، نيجيريا.

2 قسم الكيمياء الحيوية، جامعة نيجيريا، نيجيريا.

Chioma A. Anosike، جامعة نيجيريا، نيجيريا

قسم الكيمياء الحيوية، جامعة نيجيريا، نيجيريا.

Lawrence U.S. Ezeanyika، جامعة نيجيريا، نيجيريا

قسم الكيمياء الحيوية، جامعة نيجيريا، نيجيريا.

Kemal Yelekçi، جامعة قادر هاس، تركيا

قسم المعلوماتية الحيوية وعلم الوراثة ، كلية الهندسة والعلوم الطبيعية ، جامعة قادر هاس، تركيا

Abdullahi Ibrahim Uba، مركز بكين لبحوث العلوم الحاسوبية، الصين

قسم النظم المعقدة، مركز بكين لبحوث العلوم الحاسوبية، الصين

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التنزيلات

منشور

2022-06-01

كيفية الاقتباس

Babandi, A. ., Anosike, C. A. ., Ezeanyika, L. U. ., Yelekçi, K. ., & Uba, A. I. . (2022). دراسات النمذجة الجزيئية لبعض النباتات النباتية من جزء Ficus sycomorus كمثبطات محتملة لإنزيم السيتوكروم CYP6P3 من Anopheles coluzzi. Jordan Journal of Pharmaceutical Sciences, 15(2), 258–275. https://doi.org/10.35516/jjps.v15i2.324

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