TY - GEN
T1 - Auto dock-based incremental docking protocol to improve docking of large ligands
AU - Dhanik, Ankur
AU - McMurray, John S.
AU - Kavraki, Lydia
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012
Y1 - 2012
N2 - It is well known that computer-aided docking of large ligands, with many rotatable bonds, is extremely difficult. AutoDock is a widely used docking program that can dock small ligands, with upto 5 or 6 rotatable bonds, accurately and quickly. Docking of larger ligands, however, is not very accurate and is computationally expensive. In this paper we present an AutoDock-based incremental docking protocol which docks a large ligand to its target protein in increments. A fragment of the large ligand is first chosen and then docked. Best docked conformations are incrementally grown and docked again, and this process is repeated until all the atoms of the ligand are docked. Each docking operation is performed using AutoDock. However, in each docking operation only a small number of rotatable bonds are allowed to rotate. We did a systematic docking study on a dataset of 73 protein-ligand complexes derived from the core set of PDBbind database. The number of rotatable bonds in the ligands vary from 7 to 30. Docking experiments were done to evaluate the docking performance of the incremental protocol in comparison to AutoDock's standard protocol. Results from the study show that, on average over the dataset, docking of large ligands using our incremental protocol is 23-fold computationally faster than docking using AutoDock's standard protocol and also has comparable or better accuracy. We propose that, for docking large ligands, our incremental protocol can be used as an alternative to AutoDock's standard protocol.
AB - It is well known that computer-aided docking of large ligands, with many rotatable bonds, is extremely difficult. AutoDock is a widely used docking program that can dock small ligands, with upto 5 or 6 rotatable bonds, accurately and quickly. Docking of larger ligands, however, is not very accurate and is computationally expensive. In this paper we present an AutoDock-based incremental docking protocol which docks a large ligand to its target protein in increments. A fragment of the large ligand is first chosen and then docked. Best docked conformations are incrementally grown and docked again, and this process is repeated until all the atoms of the ligand are docked. Each docking operation is performed using AutoDock. However, in each docking operation only a small number of rotatable bonds are allowed to rotate. We did a systematic docking study on a dataset of 73 protein-ligand complexes derived from the core set of PDBbind database. The number of rotatable bonds in the ligands vary from 7 to 30. Docking experiments were done to evaluate the docking performance of the incremental protocol in comparison to AutoDock's standard protocol. Results from the study show that, on average over the dataset, docking of large ligands using our incremental protocol is 23-fold computationally faster than docking using AutoDock's standard protocol and also has comparable or better accuracy. We propose that, for docking large ligands, our incremental protocol can be used as an alternative to AutoDock's standard protocol.
KW - AutoDock
KW - PDBbind
KW - computer-aided docking
KW - docking programs
KW - drug design
KW - drug discovery
KW - fast docking
KW - high-dimensional conformation spaces
KW - large flexible ligands
KW - protein-ligand complexes
UR - http://www.scopus.com/inward/record.url?scp=84871180401&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84871180401&partnerID=8YFLogxK
U2 - 10.1109/BIBMW.2012.6470370
DO - 10.1109/BIBMW.2012.6470370
M3 - Conference contribution
AN - SCOPUS:84871180401
SN - 9781467327466
T3 - Proceedings - 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012
SP - 48
EP - 55
BT - Proceedings - 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012
T2 - 2012 IEEE International Conference on Bioinformatics and Biomedicine Workshops, BIBMW 2012
Y2 - 4 October 2012 through 7 October 2012
ER -