How similar is your antibody to clinical-stage therapeutics?
- To use this application, you only require an amino acid antibody variable domain heavy and light chain sequence.
- The Therapeutic Antibody Profiler (TAP) compares your antibody variable domain sequence against five developability guidelines derived from clinical-stage therapeutic values.
- TAP uses ABodyBuilder, with side-chains modelled by PEARS, to generate a model structure of your antibody. The standard implementation takes around 30 seconds.
- If the H3 loop can not be modelled using FREAD, it defaults to modelling the loop with MODELLER (+~3mins). Sphinx can also be used for more accurate modelling, but expect a large increase in runtime.
- TAP then calculates the following properties (explained in the paper) to see if your antibody design is commenserate with those of clinical-stage therapeutics:
- Total CDR Length
- Patches of Surface Hydrophobicity (PSH) metric across the CDR Vicinity
- Patches of Positive Charge (PPC) metric across the CDR Vicinity
- Patches of Negative Charge (PNC) metric across the CDR Vicinity
- Structural Fv Charge Symmetry Parameter (SFvCSP)
- TAP also outputs...
- An interactive representation of your antibody model, allowing you to visualise hydrophobic/charge patches on the Van der Waals surface. The model is downloadable.
- A representation showing predicted model accuracy, communicating the confidence you should have in our metric values
- Sequence liabilities likely to lead to post- or co-translational modification
- North-defined length-independent canonical forms (excluding the H3 loop)
- For a sample TAP output, please click here. More information about the guidelines and more resources can be found here.
For a full description of the profiler, or if you use this software, please refer to: Raybould MIJ, et al. Five Computational Developability Guidelines for Therapeutic Antibody Profiling. PNAS. (2019)
Please cite our paper "Five Computational Developability Guidelines for Therapeutic Antibody Profiling" if making use of these datasets.
- The 242 Clinical-Stage Therapeutics (CST) models that set the TAP Guidelines in the PNAS paper can be found here.
- The 242 CST sequences can be found in the paper SI here (Dataset S2).
- The TAP Guidelines were last updated on 4th May 2021. We are now tracking 526 post Phase-I therapeutic Fvs. The 526 models that set the most recent TAP Guidelines can be found here. Their TAP metric values can be found here. The guidelines set by these models are below.
NB: The PSH value has shifted upwards for both CSTs and natural antibodies with a recent code change to include previously omitted residues in the periphery of the CDR vicinity. This code change came into effect on 4th May 2021, please recalculate TAP metrics for your antibodies if interpreting relative to these reference values. See the new Vander Heiden natural antibody values here [as an indication, PSH 95th percentile: 190.27 (CSTs: 173.52), PSH 100th percentile: 248.38 (CSTs: 208.67)]:
| Property | Amber Region (4th May 2021) | Red Region (4th May 2021) |
|---|---|---|
| Total CDR Length (L) | 37 ≤ L ≤ 43 | L < 37 |
| 55 ≤ L ≤ 63 | L > 63 | |
| Patches of Surface Hydrophobicity (PSH) | 89.9 ≤ PSH ≤ 116.3 | PSH < 89.9 |
| 173.52 ≤ PSH ≤ 208.67 | PSH > 208.67 | |
| Patches of Positive Charge (PPC) | 1.26 ≤ PPC ≤ 3.74 | PPC > 3.74 |
| Patches of Negative Charge (PNC) | 1.84 ≤ PNC ≤ 4.25 | PNC > 4.25 |
| Structural Fv Charge Symmetry Parameter (SFvCSP) | -19.50 ≤ SFvCSP ≤ -5.7 | SFvCSP < -19.50 |
Please visit Thera-SAbDab to access our latest CST sequence data.
