M-ZDOCK: A grid-based approach for Cn symmetric multimer docking

Bioinformatics Program, Boston University, Boston, MA, USA.
Bioinformatics (Impact Factor: 4.98). 05/2005; 21(8):1472-8. DOI: 10.1093/bioinformatics/bti229
Source: PubMed


Computational protein docking is a useful technique for gaining insights into protein interactions. We have developed an algorithm M-ZDOCK for predicting the structure of cyclically symmetric (Cn) multimers based on the structure of an unbound (or partially bound) monomer. Using a grid-based Fast Fourier Transform approach, a space of exclusively symmetric multimers is searched for the best structure. This leads to improvements both in accuracy and running time over the alternative, which is to run a binary docking program ZDOCK and filter the results for near-symmetry. The accuracy is improved because fewer false positives are considered in the search, thus hits are not as easily overlooked. By searching four instead of six degrees of freedom, the required amount of computation is reduced. This program has been tested on several known multimer complexes from the Protein DataBank, including four unbound multimers: three trimers and a pentamer. For all of these cases, M-ZDOCK was able to find at least one hit, whereas only two of the four testcases had hits when using ZDOCK and a symmetry filter. In addition, the running times are 30-40% faster for M-ZDOCK. AVAILABILITY: M-ZDOCK is freely available to academic users at CONTACT: SUPPLEMENTARY INFORMATION:

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    • "We limited our modeling to EC1– EC3, for which we have determined crystal structures and have identified specificity-determining residues. We used the M-zdock program (Pierce et al., 2005) to produce symmetric homodimeric models for the EC1–EC3 domain regions of PcdhaC2, Pcdhb1, PcdhgA8, and PcdhgC5. We generated thousands of models for each crystal structure and used the experimentally identified specificity determinant residues to filter the docked models; requiring models to include these residues at the binding interface. "
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    Cell 10/2015; 163(3). DOI:10.1016/j.cell.2015.09.026 · 32.24 Impact Factor
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    • "Only a small number methods exist for docking more than two monomers. These methods attempt to make the search for the correct docking configuration tractable by focusing on symmetric complexes [10] or by extending pairwise solutions via combinatorially assembling monomers incrementally, using greedy heuristics to cut down the search space such as selecting only a subset of the complexes of size k and pass them to the next stage as candidates to search for a complex of size k + 1, or generating pairwise docking results and expanding them using a minimum spanning tree [11,12]. "
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    BMC Structural Biology 11/2013; 13 Suppl 1(Suppl 1):S7. DOI:10.1186/1472-6807-13-S1-S7 · 1.18 Impact Factor
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    • "The assembly of the modelled MCU subunits was performed using the symmetric multimer docking program M - ZDOCK ( Pierce et al , 2005 ) . Channel forming proposed solutions were analysed and the best scoring ones , according to energetic criteria , have been subjected to a simulated annealing minimization using Yasara Structure Suite ( v . "
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