TY - JOUR
T1 - PRISM-EM
T2 - Template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps
AU - Kuzu, Guray
AU - Keskin, Ozlem
AU - Nussinov, Ruth
AU - Gursoy, Attila
PY - 2016
Y1 - 2016
N2 - The structures of protein assemblies are important for elucidating cellular processes at the molecular level. Three-dimensional electron microscopy (3DEM) is a powerful method to identify the structures of assemblies, especially those that are challenging to study by crystallography. Here, a new approach, PRISM-EM, is reported to computationally generate plausible structural models using a procedure that combines crystallographic structures and density maps obtained from 3DEM. The predictions are validated against seven available structurally different crystallographic complexes. The models display mean deviations in the backbone of <5 Å. PRISM-EM was further tested on different benchmark sets; the accuracy was evaluated with respect to the structure of the complex, and the correlation with EM density maps and interface predictions were evaluated and compared with those obtained using other methods. PRISM-EM was then used to predict the structure of the ternary complex of the HIV-1 envelope glycoprotein trimer, the ligand CD4 and the neutralizing protein m36.
AB - The structures of protein assemblies are important for elucidating cellular processes at the molecular level. Three-dimensional electron microscopy (3DEM) is a powerful method to identify the structures of assemblies, especially those that are challenging to study by crystallography. Here, a new approach, PRISM-EM, is reported to computationally generate plausible structural models using a procedure that combines crystallographic structures and density maps obtained from 3DEM. The predictions are validated against seven available structurally different crystallographic complexes. The models display mean deviations in the backbone of <5 Å. PRISM-EM was further tested on different benchmark sets; the accuracy was evaluated with respect to the structure of the complex, and the correlation with EM density maps and interface predictions were evaluated and compared with those obtained using other methods. PRISM-EM was then used to predict the structure of the ternary complex of the HIV-1 envelope glycoprotein trimer, the ligand CD4 and the neutralizing protein m36.
KW - PRISM-EM
KW - modelling protein assemblies
KW - multimolecular protein complexes
KW - protein structure prediction
KW - threedimensional electron microscopy
UR - http://www.scopus.com/inward/record.url?scp=84992699762&partnerID=8YFLogxK
U2 - 10.1107/S2059798316013541
DO - 10.1107/S2059798316013541
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AN - SCOPUS:84992699762
SN - 0907-4449
VL - 72
SP - 1137
EP - 1148
JO - Acta Crystallographica Section D: Structural Biology
JF - Acta Crystallographica Section D: Structural Biology
ER -