title: PRISM-EM: template interface-based modelling of multi-protein complexes guided by cryo-electron microscopy density maps.
abstract: 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.
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, 34450 Istanbul, Turkey.
authors.forename: Guray
authors.initials: G
authors.lastname: Kuzu
authors.affiliation: Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, 34450 Istanbul, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Keskin
authors.affiliation: Cancer and Inflammation Program, Leidos Biomedical Research Inc., National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.affiliation: Computer Engineering, Koc University, 34450 Istanbul, Turkey.
authors.forename: Attila
authors.initials: A
authors.lastname: Gursoy
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism; D020285:Cryoelectron Microscopy / Q000379:methods*; D030562:Databases, Protein; D006678:HIV / Q000737:chemistry / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D011506:Proteins
keywords: PRISM-EM; modelling protein assemblies; multimolecular protein complexes; protein structure prediction; three-dimensional electron microscopy