Coupling an Ensemble of Homologues Improves Refinement of Protein Homology Models

2015 ◽  
Vol 11 (12) ◽  
pp. 5578-5582 ◽  
Author(s):  
André Wildberg ◽  
Dennis Della Corte ◽  
Gunnar F. Schröder
Keyword(s):  
Protein Homology ◽  
Homology Models

scholarly journals Using Protein Homology Models for Structure-Based Studies: Approaches to Model Refinement

2006 ◽  
Vol 6 ◽  
pp. 1542-1554 ◽  
Author(s):  
V. Kairys ◽  
M.K. Gilson ◽  
Miguel Xavier Fernandes
Keyword(s):  
Experimental Data ◽  
Homology Model ◽  
Target Protein ◽  
Protein Homology ◽  
Model Refinement ◽  
Sequence Identity ◽  
Computational Methodology ◽  
Backbone Atoms ◽  
Homology Models ◽  
Template Protein

Homology modeling is a computational methodology to assign a 3-D structure to a target protein when experimental data are not available. The methodology uses another protein with a known structure that shares some sequence identity with the target as a template. The crudest approach is to thread the target protein backbone atoms over the backbone atoms of the template protein, but necessary refinement methods are needed to produce realistic models. In this mini-review anchored within the scope of drug design, we show the validity of using homology models of proteins in the discovery of binders for potential therapeutic targets. We also report several different approaches to homology model refinement, going from very simple to the most elaborate. Results show that refinement approaches are system dependent and that more elaborate methodologies do not always correlate with better performances from built homology models.

scholarly journals Relative Binding Free Energy Calculations Applied to Protein Homology Models

2016 ◽  
Vol 56 (12) ◽  
pp. 2388-2400 ◽  
Author(s):  
Daniel Cappel ◽  
Michelle Lynn Hall ◽  
Eelke B. Lenselink ◽  
Thijs Beuming ◽  
Jun Qi ◽  
...  
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Protein Homology ◽  
Energy Calculations ◽  
Relative Binding ◽  
Binding Free Energy Calculations ◽  
Homology Models

Comparison of moonlighting guanylate cyclases: roles in signal direction?

2014 ◽  
Vol 42 (6) ◽  
pp. 1773-1779 ◽  
Author(s):  
Lubna Freihat ◽  
Victor Muleya ◽  
David T. Manallack ◽  
Janet I. Wheeler ◽  
Helen R. Irving
Keyword(s):  
Interleukin 1 ◽  
Structural Features ◽  
Kinase Domain ◽  
The Novel ◽  
Natural Ligands ◽  
Signalling Cascades ◽  
A Minor ◽  
Mammalian Protein ◽  
Homology Models

Over 30 receptor-like kinases contain a guanylate cyclase (GC) catalytic centre embedded within the C-terminal region of their kinase domain in the model plant Arabidopsis. A number of the kinase GCs contain both functional kinase and GC activity in vitro and the natural ligands of these receptors stimulate increases in cGMP within isolated protoplasts. The GC activity could be described as a minor or moonlighting activity. We have also identified mammalian proteins that contain the novel GC centre embedded within kinase domains. One example is the interleukin 1 receptor-associated kinase 3 (IRAK3). We compare the GC functionality of the mammalian protein IRAK3 with the cytoplasmic domain of the plant prototype molecule, the phytosulfokine receptor 1 (PSKR1). We have developed homology models of these molecules and have undertaken in vitro experiments to compare their functionality and structural features. Recombinant IRAK3 produces cGMP at levels comparable to those produced by PSKR1, suggesting that IRAK3 contains GC activity. Our findings raise the possibility that kinase-GCs may switch between downstream kinase-mediated or cGMP-mediated signalling cascades to elicit desired outputs to particular stimuli. The challenge now lies in understanding the interaction between the GC and kinase domains and how these molecules utilize their dual functionality within cells.

Comparison of homology models and crystal structures of cuticle‐degrading proteases from nematophagous fungi: structural basis of nematicidal activity

2011 ◽  
Vol 25 (6) ◽  
pp. 1894-1902 ◽  
Author(s):  
Lianming Liang ◽  
Shuqun Liu ◽  
Jinkui Yang ◽  
Zhaohui Meng ◽  
Liping Lei ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Nematophagous Fungi ◽  
Nematicidal Activity ◽  
Structural Basis ◽  
Homology Models
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