A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.
Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins.
Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E19-502b, Cambridge, MA 02139, USA.
Neeraj J
NJ
Agrawal
Novartis Pharma AG, CH-4057 Basel, Switzerland.
Bernhard
B
Helk
Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E19-502b, Cambridge, MA 02139, USA. Electronic address: trout@mit.edu.
Bernhardt L
BL
Trout
D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D018793:Interleukin-13 / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
D018793:Interleukin-13; D011506:Proteins
Molecular simulation; Protein engineering; Protein interaction; Spatial interaction map; Structure-based tool