دورية أكاديمية
Incorporating NOE-Derived Distances in Conformer Generation of Cyclic Peptides with Distance Geometry.
| العنوان: | Incorporating NOE-Derived Distances in Conformer Generation of Cyclic Peptides with Distance Geometry. |
|---|---|
| المؤلفون: | Wang S; Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, Switzerland., Krummenacher K; Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, Switzerland., Landrum GA; Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, Switzerland., Sellers BD; Department of Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Di Lello P; Department of Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Robinson SJ; Department of Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Martin B; Department of Structural Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States., Holden JK; Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, California 94080, United States., Tom JYK; Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, California 94080, United States., Murthy AC; Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, California 94080, United States., Popovych N; Department of Early Discovery Biochemistry, Genentech, Inc., South San Francisco, California 94080, United States., Riniker S; Laboratory of Physical Chemistry, ETH Zürich, Vladimir-Prelog-Weg 2, 8093 Zürich, Switzerland. |
| المصدر: | Journal of chemical information and modeling [J Chem Inf Model] 2022 Feb 14; Vol. 62 (3), pp. 472-485. Date of Electronic Publication: 2022 Jan 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101230060 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-960X (Electronic) Linking ISSN: 15499596 NLM ISO Abbreviation: J Chem Inf Model Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Chemical Society, c2005- |
| مواضيع طبية MeSH: | Peptides* , Peptides, Cyclic*, Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy/methods ; Models, Molecular ; Protein Conformation |
| مستخلص: | Nuclear magnetic resonance (NMR) data from NOESY (nuclear Overhauser enhancement spectroscopy) and ROESY (rotating frame Overhauser enhancement spectroscopy) experiments can easily be combined with distance geometry (DG) based conformer generators by modifying the molecular distance bounds matrix. In this work, we extend the modern DG based conformer generator ETKDG, which has been shown to reproduce experimental crystal structures from small molecules to large macrocycles well, to include NOE-derived interproton distances. In noeETKDG, the experimentally derived interproton distances are incorporated into the distance bounds matrix as loose upper (or lower) bounds to generate large conformer sets. Various subselection techniques can subsequently be applied to yield a conformer bundle that best reproduces the NOE data. The approach is benchmarked using a set of 24 (mostly) cyclic peptides for which NOE-derived distances as well as reference solution structures obtained by other software are available. With respect to other packages currently available, the advantages of noeETKDG are its speed and that no prior force-field parametrization is required, which is especially useful for peptides with unnatural amino acids. The resulting conformer bundles can be further processed with the use of structural refinement techniques to improve the modeling of the intramolecular nonbonded interactions. The noeETKDG code is released as a fully open-source software package available at www.github.com/rinikerlab/customETKDG. |
| المشرفين على المادة: | 0 (Peptides) 0 (Peptides, Cyclic) |
| تواريخ الأحداث: | Date Created: 20220114 Date Completed: 20220324 Latest Revision: 20220324 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1021/acs.jcim.1c01165 |
| PMID: | 35029985 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1549-960X |
|---|---|
| DOI: | 10.1021/acs.jcim.1c01165 |