HotPatch Web Gateway

Statistical Analysis of Unusual Patches on Protein Surfaces


HotPatch finds unusual patches on the surface of proteins, and computes just how unusual they are (patch rareness), and how likely each patch is to be of functional importance (functional confidence (FC).) The statistical analysis is done by comparing your protein's surface against the surfaces of a large set of proteins whose functional sites are known.

INPUT: Upload your PDB file as input:  
(Maximum uploaded file size: 1.5 MB.)

PROTEIN FUNCTION TYPE: If you already know your protein's function type, you can compare against just a sub-population of proteins with that particular type of functional site.

(If you don't know your protein's function type, or you just want to compare it against proteins in general, choose "Generic".)

Choose One Protein Function:
 Generic Functional Site [gf] info?  Protein Binding (Non-Catalytic) [pb] info?
 Catalytic (General) Site [cg] info?  Oligomeric Interfaces [ol] info?
 Hydrolases [hy] info?  Metal Ion-Binding Sites [mp] info?
 Proteases [pr] info?  Interact w/DNA or RNA (catalytic or not) [dn] info?
 Transferases [tr] info?  Interact w/Small Molecules (catalytic or not) [sm] info?
 Kinases [ki] info?  Interact w/Lipids (catalytic or not) [lp] info?
 Oxidoreductases [or] info?  Interact w/Carbohydrates (catalytic or not) [cm] info?

SURFACE PROPERTIES: HotPatch can find statistically significant patches with high values of particular properties on the surfaces of proteins.

Choose One or More Properties: (If you choose more than one property, you get multiple email responses.)
 Neural Network combination info?  Concavity info?
 Electrostatic Potential info?  Negative Potential info?
 Hydrophobicity info?  Hydrophilicity info?
 Surface Roughness info?   

Note that when you chose a protein function type above, here the checkbox for the best predictor property(ies) appropriate for that function gets checked automatically, and other properties will change color based on their relative usefuless as predictors-- from green for best to yellow for decent to red for worst. (Try changing protein function back & forth to see the change.) Sometimes it is of physical interest to evaluate properties that are decent even though their predictions are not the most accurate, so you are free to check those if you want to evaluate them. If you choose properties that are bad predictors for that function type, we can't ensure the accuracy of the resulting predictions.

Size constraints: For each property you check, you will receive one email at least twice the size of your input PDB file, so your email inbox must be large enough to fit them. For electrostatic and neural network properties, the maximum number of non-hydrogen atoms allowed is 15900. For all other properties, the maximum is 32000 atoms. Max. upload file size is 1.5 MB.

HETEROATOMS: HotPatch has been trained on structures of known function with substrates removed, but cofactors left in. In most cases substrates are heteroatoms (non-protein). HotPatch cannot automatically identify substrates that are protein chains (we recommend you manually remove protein substrates from your uploaded file), but the program can automatically ignore heteroatoms.
Do you want HotPatch to ignore all heteroatoms?
 Ignore Heteroatoms  Include Heteroatoms

VISUALIZATION SCRIPT: Optionally, HotPatch can also write a script that will display the patches on the structure, when the script is loaded into some common molecular visualization programs. If you want a script, choose what type.
 None  RasMol
 PyMol  DS Viewer (formerly WebLab Viewer)

OUTPUT: HotPatch generates complete statistics (functional confidence and patch rareness) on the most significant patches on your protein. For each property you choose to analyze, you'll receive an email to which will be attached:

  1. a PDB-format file in which atomic B-factors (temp. factors) are replaced by patch indices; and the PDB file's Header Remarks will give statistical scores.
  2. a PDB-format file in which atomic B-factors are replaced by the raw values of the property used for patch analysis (for example, hydrophobicity instead of hydrophobic patches).

Email address to send results:
Your email inbox must have enough room to hold a mail somewhat more than twice the size of your input PDB file, for each property you choose to compute.