کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2076786 | 1079464 | 2008 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Selection and flexible optimization of binding modes from conformation ensembles
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موضوعات مرتبط
مهندسی و علوم پایه
ریاضیات
مدلسازی و شبیه سازی
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چکیده انگلیسی
This paper describes a new semi-flexible docking approach named Fado (flexible alignment and docking), which incorporates flexibility by using an ensemble of precomputed ligand conformers. A primary ligand is defined as a linear combination over all input conformers. An optimization with regard to the linear coefficients makes the ligand flexible. Initially, a point matching problem utilizing the Merck Molecular Force Field (MMFF) is modeled in order to compute the correct orientation of the ligand with respect to the target. The problem is then solved through a local optimization approach (RPROP). This is done for 20 randomized ligand orientations, yielding 20 binding modes per complex. Evaluating these modes illustrates that our method is able to reproduce the binding modes of molecules within a few minutes of CPU time. A representative dataset of diverse protein-ligand complexes could be reproduced with 78% accuracy below 2Â Â Ã
RMSD distance to the reference crystal structure. Fado is available upon request to the authors (see also http://www.zib.eu/Numerik/projects/docking/projectlong.en.html).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biosystems - Volume 92, Issue 1, April 2008, Pages 42-48
Journal: Biosystems - Volume 92, Issue 1, April 2008, Pages 42-48
نویسندگان
A. Guerler, S. Moll, M. Weber, H. Meyer, F. Cordes,