Document Detail


A solvated ligand rotamer approach and its application in computational protein design.
MedLine Citation:
PMID:  23192355     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The structure-based design of protein-ligand interfaces with respect to different small molecules is of great significance in the discovery of functional proteins. By statistical analysis of a set of protein-ligand complex structures, it was determined that water-mediated hydrogen bonding at the protein-ligand interface plays a crucial role in governing the binding between the protein and the ligand. Based on the novel statistic results, a solvated ligand rotamer approach was developed to explicitly describe the key water molecules at the protein-ligand interface and a water-mediated hydrogen bonding model was applied in the computational protein design context to complement the continuum solvent model. The solvated ligand rotamer approach produces only one additional solvated rotamer for each rotamer in the ligand rotamer library and does not change the number of side-chain rotamers at each protein design site. This has greatly reduced the total combinatorial number in sequence selection for protein design, and the accuracy of the model was confirmed by two tests. For the water placement test, 61 % of the crystal water molecules were predicted correctly in five protein-ligand complex structures. For the sequence recapitulation test, 44.7 % of the amino acid identities were recovered using the solvated ligand rotamer approach and the water-mediated hydrogen bonding model, while only 30.4 % were recovered when the explicitly bound waters were removed. These results indicated that the developed solvated ligand rotamer approach is promising for functional protein design targeting novel protein-ligand interactions.
Authors:
Xiaoqiang Huang; Ji Yang; Yushan Zhu
Related Documents :
24548275 - The cysteine desulfurase iscs of mycobacterium tuberculosis is involved in iron-sulfur ...
23086935 - Poly-small ubiquitin-like modifier (polysumo)-binding proteins identified through a str...
24072065 - Solvent interaction analysis of intrinsically disordered proteins in aqueous two-phase ...
23670815 - Classification of efflux proteins using efficient radial basis function networks with p...
6611865 - Covalent dna-protein crosslinking occurs after hyperthermia and radiation.
293655 - Photoreactive labeling of m13 coat protein in model membranes by use of a glycolipid pr...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-29
Journal Detail:
Title:  Journal of molecular modeling     Volume:  -     ISSN:  0948-5023     ISO Abbreviation:  J Mol Model     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9806569     Medline TA:  J Mol Model     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Chemical Engineering, Tsinghua University, Beijing, 100084, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Dimerization and bifunctionality confer robustness to the isocitrate dehydrogenase regulatory system...
Next Document:  Resveratrol worsens survival in SCID mice with prostate cancer xenografts in a cell-line specific ma...