Utilities
Documentation -> Background
FAQ
About
Utilities
Documentation -> Background
FAQ
About
PoPS is a software tool for modeling protease activity. Its main aim is to provide an environment in which the user can learn and reason about the activity of any protease. PoPS allows the user to create a model of activity for an arbitrary protease by specifying general parameters that are commonly used to describe the function of a protease, for example, the number of important subsites, their amino acid preferences and the relative importance of the subsites. (For more information about these parameters, see the section below. The user can then supply a substrate (protein sequence) and PoPS will use the protease model to predict where the substrate will be cleaved.
A simple prediction of cleavages is very useful in itself, particularly if the protease has a well-defined activity. In addition, the predictions don't just include what will happen, but also what will not happen. However, PoPS's utility does not end here. Once a prediction has been made, PoPS allows the user to adjust parameters and the original protease model to perform a deeper investigation of how the protease is functioning. For example, in the case of a protease whose function is poorly defined, predictions can be compared to experimental results, and the model can be altered to gain a better understanding of the true model of the protease's activity.
PoPS also aims to provide other information about the substrate that might improve the accuracy of predictions. At the moment this includes tertiary structure and secondary structure predictions, but more options are currently being implemented.
Because accessing information about protease specificity can be difficult, particularly for non-experts, PoPS has a publicly accessible models database that allows people to share their specificity models. Using a simple login procedure, anyone can deposit a model in the database, and include extra information such as bibliographic details and comments.
Finally, we are constantly developing 'helper' tools that can assist users. Such tools include visual comparisons of how models perform, and a tool to plot a ROC curve to measure how well a model performs. All these accessory tools can be found on the utilities page.
The Role of Subsites in Substrate Cleavage, and the P/P' & S/S' Notation
The following information is an informal presentation of the notation of enzyme/substrate interaction as proposed by Schechter and Berger (Biochemical and Biophysical Research Communications, vol 27, no 2, 1967, pp 157-162).
A protease has a number of subsites which it uses to recognise and bind to a small section of a protein substrate. For example, the enzyme in the diagram below has 4 subsites, which it uses to bind to the amino acids K, S, R and A.
There are a number of factors that influence whether a protease will bind to a substrate. One of the most important factors is the amino acids present in the substrate sequence where the protease subsites make contact. Each subsite of the protease has a particular preference for the size, charge and shape of the R group of the amino acid contacting the subsite. Sometimes this preference is highly specific for the R group, accepting only one or a few specific amino acids. In other instances, a subsite may be less specific, only requiring that there be an amino acid at that position, but not having any preference for its type. In addition to the specificity for the R group, each subsite might have a relative importance compared to the other subsites. In some cases, the requirements of a subsite must always be met for a cleavage to occur, whereas in the case of other subsites, even if their requirements are not fulfilled, a cleavage may still occur.
Once the protease has bound the substrate, it can cleave the
protein sequence between two of the amino acids. This point of
cleavage is known as the scissile bond. Within the substrate, the
amino acid immediately N-terminal to the scissile bond is referred to
as P1, while the amino acid immediately C-terminal to the scissile
bond is referred to as P1'. The amino acids alongside the cleavages
are incrementally numbered as they approach the ends of the protein.
Similarly, the subsite containing the P1 residue is known as the S1
subsite, and the subsite containing the P1' subsite is known as the
S1' subsite. The subsites are numbered in increasing order moving
away from the scissile bond. In the following example, the protease
has 4 subsites, but note that PoPS allows users to define any number
of subsites in a model.
This diagram shows the structure of PoPS, indicating how the modules interact, and where they are located.
Utilities
Documentation -> Background
FAQ
About
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