FRODOCK Interactive protein-protein docking

This web service is for the structural prediction of protein-protein interactions using an improved version of our Fast Rotational DOCKing method*. Given the 3D coordinates of two interacting proteins (conforming PDB format) the server generates very efficiently many potential predictions of how they could interact. Once your job is completed you can interactively check protein-protein models and add experimental constraints to refine the docking. A standard-size case usually takes only a couple of minutes to complete the docking depending of the size and computational resources available. The users can choose between scoring weighting schemes optimized for three different interaction types: Enzyme/Substrate, Antibody/Antigen, and Others to slightly improve the success rates. Please keep track of your jod ID number so you can have access to your results from the Results tab. Alternatively you can also choose to be notified by email.

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*If you would like to refer our work use:
Server/Improved method E. Ramírez-Aportela, J.R. López-Blanco, and P. Chacón (2016). FRODOCK 2.0: Fast Protein-Protein docking server. Bioinformatics, 32(15), 2386-2388. (Please, use this reference)
Original method J.I. Garzón, J.R. López-Blanco, C. Pons, J. Kovacs, R. Abagyan, J. Fernández-Recio, and P. Chacón (2009). FRODOCK: a new approach for fast rotational protein-protein docking. Bioinformatics, 25, 2544-2551.

or select an example

Here you can find the best docking results found in Benchmark 4.0. If you click on any of the case links, an interactive Jmol showing the first acceptable solution and the bound ligand pose will appear.

Antigen/Antibody (1FSK)
Enzyme/Substrate (1JTG)
Others (1GPW)

Here you can find all the best docking results found in Benchmark 4.0.

Antigen/Antibody (25)
PDB* Rank* Total
RMSD
Interface
RMSD
Fnat Fnot
1AHW 32.461.080.660.22
1BVK 18.193.800.171.08
1DQJ 2636.593.470.230.30
1E6J 78.244.050.270.61
1JPS 14.630.950.510.08
1MLC 44.721.110.770.21
1VFB 56.974.010.170.94
1WEJ 11.570.770.740.26
2FD6 110.873.160.300.74
2I25 378.123.190.190.33
2VIS 1217.703.040.201.04
1BJ1 104.691.420.570.10
1FSK 11.530.660.850.06
1I9R 28.081.650.610.15
1IQD 28.202.360.400.35
1K4C 3299.324.010.130.44
1KXQ 12.961.020.860.20
1NCA 92.310.720.820.13
1NSN 295.092.610.430.57
1QFW 53.141.210.790.13
2QFW 12.361.420.730.16
2JEL 107.914.460.160.39
1BGX -----
1E4K 6424.153.840.270.42
2HMI 29645.643.930.210.50
Enzyme/Substrate (52)
PDB* Rank* Total
RMSD
Interface
RMSD
Fnat Fnot
1AVX 12.210.800.750.17
1AY7 33.181.100.620.12
1BVN 12.361.360.550.26
1CGI 96.584.090.120.36
1CLV 35.032.510.310.34
1D6R 378.734.000.100.76
1DFJ 14.071.870.600.75
1E6E 17.992.670.300.56
1EAW 153.921.350.740.39
1EWY 98.685.000.150.90
1EZU 258.852.670.390.38
1F34 45.141.900.520.29
1FLE 155.902.670.240.45
1GL1 18.964.170.110.45
1GXD 13315.903.650.130.44
1HIA 28.824.180.141.22
1JTG 10.860.600.710.32
1MAH 12.370.970.780.49
1N8O 32.381.190.670.04
1OC0 8179.053.890.150.76
1OPH 29410.003.900.610.65
1OYV 44.121.410.650.43
BOYV 56778.8913.390.420.48
1PPE 10.840.530.870.27
1R0R 28.742.440.580.71
1TMQ 183.991.990.570.66
1UDI 46.993.370.250.52
1YVB 1811.462.110.340.29
2ABZ 1879.072.940.290.49
2B42 195.492.100.800.84
2J0T 6811.143.880.171.52
2MTA 612.323.800.270.98
2O8V 1889.933.980.190.24
2OUL 11.990.860.850.29
2PCC 109.654.010.331.23
2SIC 527.731.620.590.41
2SNI 35.571.620.710.50
2UUY 1717.833.920.140.47
3SGQ 499.162.440.450.59
7CEI 18.322.480.530.55
1ACB 1111.393.820.170.90
1IJK 6788.872.580.310.60
1JIW 2097.854.060.170.56
1KKL 678.794.560.140.58
1M10 859.674.850.140.45
1NW9 207.408.850.100.88
4CPA 104.601.650.830.94
1F6M 38719.926.470.211.23
1FQ1 23769.324.220.210.15
1PXV 489.314.750.240.45
1ZLI -----
2O3B 47910.493.990.240.94
Others (99)
PDB* Rank* Total
RMSD
Interface
RMSD
Fnat Fnot
1A2K 1149.143.180.260.42
1AK4 429.964.070.280.63
1AKJ 178.634.850.221.73
1AZS 37.022.030.560.39
1B6C 12.572.070.800.32
1BUH 404.092.420.320.23
1E96 111.143.540.231.10
1EFN 27213.393.510.380.33
1F51 69.775.010.130.89
1FC2 2489.915.000.190.28
1FCC 11948.654.160.230.51
1FFW 110.593.380.440.33
1FQJ 177.283.100.370.30
1GCQ 331.731.030.710.10
1GHQ 159417.003.960.521.44
1GLA 2519.103.920.181.21
1GPW 12.031.240.790.50
1H9D 178.094.160.180.27
1HCF 85.361.890.390.59
1HE1 998.4714.850.160.33
1I4D 8617.603.750.110.82
1J2J 19.573.390.240.73
1JWH 2011.522.280.320.38
1K74 12.000.990.750.15
1KAC 1110.373.830.360.54
1KLU 176610.042.980.350.42
1KTZ 2618.262.270.450.26
1KXP 111.563.980.300.26
1ML0 12.641.360.710.37
1OFU 1214.392.780.390.31
1PVH 135814.953.500.140.39
1QA9 198.343.450.380.81
1RLB 57.921.970.690.52
1RV6 12.881.500.680.40
1S1Q 336.123.130.260.79
1SBB 17313.400.850.790.61
1T6B 1458.172.550.540.23
1US7 4112.453.990.210.71
1WDW 11.711.530.520.21
1XD3 18.503.030.130.24
1XU1 957.292.520.470.26
1Z0K 19.153.790.130.46
1Z5Y 17.272.880.310.46
1ZHH 219.213.180.190.28
1ZHI 93.190.970.730.27
2A5T 4575.813.840.230.88
2A9K 5213.812.960.180.27
2AJF 33615.943.960.170.56
2B4J 949.114.540.690.50
2BTF 106.753.320.180.44
2FJU 2498.923.680.310.84
2G77 17.602.670.350.20
2HLE 13.681.860.440.26
2HQS 36211.823.710.320.49
2OOB 8712.173.300.390.43
2OOR 18012.273.790.260.50
2VDB 23.000.950.730.03
3BP8 179.692.860.310.94
3D5S 13.871.710.460.27
1GP2 112.482.670.100.18
1GRN 73.221.670.390.26
1HE8 5918.294.470.181.34
1I2M 17.004.420.170.60
1IB1 1399.974.170.110.70
1K5D 95.992.550.150.20
1LFD 78.674.920.380.43
1MQ8 6624.943.990.300.93
1N2C 88.084.170.170.24
1R6Q 112.783.810.390.57
1SYX 13.852.400.500.22
1WQ1 1210.773.360.320.45
1XQS 210.873.020.290.11
2AYO 16.112.910.250.33
2CFH 73.312.180.340.50
2H7V 19818.663.550.540.17
2HRK 556.312.810.520.37
2J7P 38769.485.420.100.39
2NZ8 89.995.580.180.62
2OZA 59.334.530.250.73
2Z0E 69.813.580.190.37
3CPH 911.063.620.130.36
1ATN 849.834.500.310.22
1BKD 146.394.570.170.52
1DE4 13.472.710.460.32
1EER 649.724.620.240.39
1FAK -----
1H1V -----
1IBR -----
1IRA -----
1JK9 14.772.800.520.07
1JMO -----
1JZD 146.533.320.300.16
1R8S -----
1Y64 -----
1ZM4 27.972.800.600.46
2C0L 33919.934.140.140.51
2I9B 11098.635.010.110.38
2IDO 429.604.630.170.72
2OT3 809.045.240.110.24

First, upload the input coordinates of both ligand (smallest) and receptor (biggest) proteins in strict PDB format. Be aware of missing atoms, alternative conformations, bad placed atoms, and a long etc. that can eventually jeopardize your results. Use your favorite PDB checker (e.g. Molprobity) to anticipate and fix any potential PDB error. You can optionally introduce an email address to receive a direct link to access your results later.


Alternatively, depending of the nature of your interaction you could choose between Enzyme/Substrate, Antibody/Antigen, and Others to slightly improve the success rates. Otherwise, Unknown interaction type will be assumed.


Upon pressing the "Submit Job" button your job will be queued in our system and you will be redirected to the Queue tab. A standard-sized docking usually takes less than two minutes to complete depending on the size and computational resources available.

Please keep track of your jod ID number so you can inspect your results by input this ID in the Results tab. Results will be available for at least two months.

Here all jobs submited to Frodock Server are listed. Your jobs are shown in darker colors whereas those submitted by others appear in lighter colors. You can check server usage and whether any queued job is running ("r" status, green) or queued ("qw" status, orange). In case any of your jobs has been queued ("qw" status) it will run as soon as computational resources become available.

Once a standard-sized job is running ("r" status) it usually takes less than two minutes to complete depending on its size. As soon as any of your jobs finishes it will move to the list of "Your finished jobs" for further access and a blinking button will appear to redirect you to the Results of the last finished job.

In case you detect any problem in any of your submitted jobs they can be easily deleted by clicking the corresponding red cross. A "dr" status (black) will evidence that it is being deleted from queue. Note that anyone but you can delete your jobs.

Once your job is completed you can interactively check protein-protein models and add experimental constraints to refine the docking. Results can be interactively visualized in 3D with JSmol. Use mouse controls to readily explore the solutions by visualizing multiple docking poses at the same time and toggling them between different molecular representations and colors. The user can choose between three different interfaces: Java, HTML5 and WebGL. The HTML5-javascript interface is activated by default. To activate the JAVA, first you must enable it in your web browser (see details) and add frodock.chaconlab.org to the exception sites in the Java panel (see details)


At the end of the page you can find the corresponding links to download all the files generated by the server.


In case you have distance constraints available, i.e. any biochemical or biophysical data indicating the approximate distance between two residues in the complex, it can be specified to select only the compatible poses and thus improve the ranking of the best solution. Please, expand the "Distance Constraints" panel and select two residues (one in the receptor and the other in the ligand), introduce the distance threshold (in Angstroms) in the input box, and click the "Add" button. You can specify up to ten distance constraints online. Finally, upon clicking on the "Apply constraints" button, a selector for the filtered solutions will appear in the "Load Solutions" panel. You can try any of the following constraints as practice.

Distance constraints examples
PDB* Interaction Type Rank Before Rank After Receptor residue Ligand residue Distance constraint
1NCA Antigen/Antibody91ASN-102THR-3195.0
1N8O Enzyme/Substrate31MET-184MET-805.0
1ZHI Others91SER-113PRO-95.0
1GCQ Others331THR-205PRO-25.0

  1. What are the common mistakes?
    Format errors are behind of FRODOCKś malfunction in 99% of the cases. Be aware of missing atoms, alternative conformations, bad placed atoms, bad names, and a long etc. that can eventually jeopardize your results. Use your favorite PDB checker (e.g. Molprobity) to anticipate and fix any potential PDB error. Ideally, the input structures should be parsed to check errors and minimized with an external program.

  2. What are the differences in the docking algorithm and/or scoring function for different Type of interaction?
    There are none algorithm differences. Depending of the protein interaction, the users can choose between scoring weighting schemes optimized for three different interaction types: Enzyme/Substrate, Antibody/Antigen, and Others to slightly improve the success rates. The normalized weighting factors for Wvdw, WEle, WSAS and, Wpair are 1.0, 0.3, 0.5,15.0 for enzyme substrate cases, 1.0, 0.6, 0.5, 15.0 for antigen-antibody cases and 1.0, 1.0, 0.5, 15.0 for Others cases, respectively. And the default parameters (unknown interaction selection) are 1.0, 0.5, 0.5, 15.0. It is important to mention that compared with the addition of the pairwise potential the gain obtained in terms of docking success rates was quite reduced. The biggest improvement (~5%) was found by up weighted the electrostatic term in test cases classified as “Others”.

  3. Do the users need to run many docking jobs with different random orientations?
    Note that the reported success rates (see ROC plots in benchmark tab) are calculated with 50 docking orientations per test case. Thus, contrary to other methods, the reported success rates give a more realistic estimation of the performance as it includes the docking dependence from initial positions. Nevertheless, FRODOCK is quite robust and when is able to identify the correct pose it does in all tested rotations. However, the exact rank of best prediction found varies; for example, for the cases in where FRODOCK found acceptable solution within 2000 positions (150 cases, success rate of 84%) we found on average a variation of 100 positions. This variation logically depends on the test case and the FRODOCK’s relative sensitivity. When FRODOCK identifies the correct pose in the top 100 the average rank variation is reduced to 15 positions. Despite of this variation and given the representativeness of the benchmark, we expect success rates as displayed in in the ROC curves in benchmark tab independently of the initial receptor and ligand orientation. Therefore, the users do not need to run many docking jobs with different random orientations.

  4. ¿Visualization problems?
    3D display is based on JSmol which is very stable and compatible with all browsers. However, problems may occur. For example, reported problems with the display of the hot spots are likely related with older version of JSmol installed in the browser cache. Please be sure that the JSmol correspond to 14.40_2015.12 ( JSmol menu >> About). If not, the solution will be to clear or empty the browser's cache

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