کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10749367 1050289 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The 340-cavity in neuraminidase provides new opportunities for influenza drug development: A molecular dynamics simulation study
ترجمه فارسی عنوان
حفره 340 در نورامینیداز فرصتی جدید برای توسعه داروهای آنفولانزا فراهم می کند: مطالعه شبیه سازی دینامیکی مولکولی
کلمات کلیدی
نورامینیداز، شبیه سازی دینامیک مولکولی، حفره 340، نقطه نقطه،
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی
Influenza neuraminidase (NA) is a pivotal target for viral infection control. However, the accumulating of mutations compromise the efficacy of NA inhibitors. Thus, it is critical to design new drugs targeted to different motifs of NA. Recently, a new motif called 340-cavity was discovered in NA subtypes close to the calcium binding site. The presence of calcium is known to influence NA activity and thermostability. Therefore, the 340-cavity is a putative ligand-binding site for affecting the normal function of NA. In this study, we performed molecular dynamics simulations of different NA subtypes to explore the mechanism of 340-loop formation. Ligand-binding site prediction and fragment library screening were also carried out to provide evidence for the 340-cavity as a druggable pocket. We found that residues G342 and P/R344 in the 340-loop determine the size of the 340-cavity, and the calcium ion plays an important role in maintaining the conformation of the 340-loop through contacts with G345 and Q347. In addition, the 340-cavity is predicted to be a ligand-binding site by metaPocket, and a sequence analysis method is proposed to predict the existence of the 340-cavity. Our study shows that the 340-cavity is not an occasional or atypical domain in NA subtypes, and it has potential to function as a new hotspot for influenza drug binding.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 470, Issue 1, 29 January 2016, Pages 130-136
نویسندگان
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