CHDOCK: a hierarchical docking approach for(4)

Then,for each rotation of the monomer subunit,an FFT-based algorithm was used to calculate the shape complementarity between the grids of the receptor and the ligand in the translational the docking calculation,an angle interval of 10° was used for rotational sampling,and a spacing of 1.2 ? was adopted in discretizing proteins onto grids for FFT-based translational distributed Euler angles were used for the rotational search,resulting in a total of 360 orientations in the rotational each rotation,up to the top 100 translations with best shape complementarities were kept and optimized by our scoring function ITScorePP(Huang and Zou 2008).The binding mode that corresponds to the best energy score in an FFT-based translational search was kept for each rotation of the ligand subunit,yielding a total of 360 ligand binding modes for a docking run.Our FFT-based docking algorithm is computationally efficient and on average can complete a full docking calculation in 30 min on a 2.6 GHZ Intel CPU core.

Scoring function

All the binding modes generated from the initial stage were evaluated by ITScorePP (Huang and Zou 2008)and minimized according to their binding scores by a SIMPLEX optimization binding energy score is a summation of the binding scores over all the interfaces between the subunits of the predicted final ranked binding modes were clustered with an RMSD cutoff of 5 ?,where the RMSD was calculated using the backbone atoms.If two binding modes have a ligand RMSD of ＜5 ?,the one with the better score is kept.

Benchmark

Based on the protein complexes in the PDB,we have also constructed a non-redundant benchmark for our symmetric protein-protein ,all the homo-oligomeric protein complexes with Cnsymmetry were collected from the crystal structures with resolution better than 2.5 ?.The symmetry type of a complex was determined by its biological unit.The symmetric homo-oligomer complexes were then clustered according to their SCOP (version 1.75) family IDs (Lo Conte et al.2000).For the complexes belonging to the same family,the one with the best resolution was selected as the representative,corresponding to a bound case of our benchmark,in which each subunit was called the bound structure of the the bound structure in each bound case,the unbound structure was identified by searching against the PDB database for the asymmetric structures using the BLASTP (proteinprotein BLAST) algorithm of the BLAST package (Camacho et al.2009).If an asymmetric structure had＞95% sequence identity with the bound structure and covered ＞95% of the sequence alignment,the asymmetric structure was regarded as a candidate of the unbound there were multiple unbound structures for a subunit protein,the one with the high resolution was selected as the yielded a total of 212 homo-oligomeric protein complexes with Cnsymmetry (http∶///SDBenchmark/) (Yan and Huang 2019).All the structures in the benchmark have their original coordinates without any random rotation.

Evaluation criteria

The quality of a predicted binding mode was measured by the ligand RMSD (LRMSD).Here,the RMSD was calculated based on the backbone atoms of the ligand subunit after optimal superimposition of the receptor subunit and the native docking performance was evaluated by the success rate,i.e.,the fraction of the targets with at least one hit in the test set when a certain number of top predictions were ,a hit is a prediction with a ligand RMSD of＜10 ? (Huang 2014).

AcknowledgementsThis work was supported by the National Key Research and Development Program of China(2016YFC and 2016YFC),the National Natural Science Foundation of China(),and the startup grant of Huazhong University of Science and Technology ().

Compliance with Ethical Standards

Conflict of interestYumeng Yan,Sheng-You Huang declare that they have no conflict of interest.

Human and animal rights and informed consentThis article does not contain any studies with human or animal subjects performed by any of the authors.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http∶///licenses/by/4.0/),which permits unrestricted use,distribution,and reproduction in any medium,provided you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.

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