TY - JOUR
T1 - FireDock
T2 - Fast interaction refinement in molecular docking
AU - Andrusier, Nelly
AU - Nussinov, Ruth
AU - Wolfson, Haim J.
PY - 2007/10
Y1 - 2007/10
N2 - Here, we present FireDock, an efficient method for the refinement and rescoring of rigid-body docking solutions. The refinement process consists of two main steps: (1) rearrangement of the interface side-chains and (2) adjustment of the relative orientation of the molecules. Our method accounts for the observation that most interface residues that are important in recognition and binding do not change their conformation significantly upon complexation. Allowing full side-chain flexibility, a common procedure in refinement methods, often causes excessive conformational changes. These changes may distort preformed structural signatures, which have been shown to be important for binding recognition. Here, we restrict side-chain movements, and thus manage to reduce the false-positive rate noticeably. In the later stages of our procedure (orientation adjustments and scoring), we smooth the atomic radii. This allows for the minor backbone and side-chain movements and increases the sensitivity of our algorithm. FireDock succeeds in ranking a near-native structure within the top 15 predictions for 83% of the 30 enzyme-inhibitor test cases, and for 78% of the 18 semi-unbound antibody-antigen complexes. Our refinement procedure significantly improves the ranking of the rigid-body PatchDock algorithm for these cases. The FireDock program is fully automated. In particular, to our knowledge, FireDock's prediction results are comparable to current state-of-the-art refinement methods while its running time is significantly lower. The method is available at http:// bioinfo3d.cs.tau.ac.il/FireDock/.
AB - Here, we present FireDock, an efficient method for the refinement and rescoring of rigid-body docking solutions. The refinement process consists of two main steps: (1) rearrangement of the interface side-chains and (2) adjustment of the relative orientation of the molecules. Our method accounts for the observation that most interface residues that are important in recognition and binding do not change their conformation significantly upon complexation. Allowing full side-chain flexibility, a common procedure in refinement methods, often causes excessive conformational changes. These changes may distort preformed structural signatures, which have been shown to be important for binding recognition. Here, we restrict side-chain movements, and thus manage to reduce the false-positive rate noticeably. In the later stages of our procedure (orientation adjustments and scoring), we smooth the atomic radii. This allows for the minor backbone and side-chain movements and increases the sensitivity of our algorithm. FireDock succeeds in ranking a near-native structure within the top 15 predictions for 83% of the 30 enzyme-inhibitor test cases, and for 78% of the 18 semi-unbound antibody-antigen complexes. Our refinement procedure significantly improves the ranking of the rigid-body PatchDock algorithm for these cases. The FireDock program is fully automated. In particular, to our knowledge, FireDock's prediction results are comparable to current state-of-the-art refinement methods while its running time is significantly lower. The method is available at http:// bioinfo3d.cs.tau.ac.il/FireDock/.
KW - Binding free energy
KW - Docking refinement
KW - Linear programming
KW - Protein-protein docking
KW - Rigid-body minimization
KW - Side-chain flexibility
UR - http://www.scopus.com/inward/record.url?scp=34548317146&partnerID=8YFLogxK
U2 - 10.1002/prot.21495
DO - 10.1002/prot.21495
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C2 - 17598144
AN - SCOPUS:34548317146
SN - 0887-3585
VL - 69
SP - 139
EP - 159
JO - Proteins: Structure, Function and Genetics
JF - Proteins: Structure, Function and Genetics
IS - 1
ER -