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webPIPSA

Protein Interaction Property Similarity Analysis


Documentation of webPIPSA

Disclaimer

This document provides a documentation of webPIPSA. For a documentation of the stand-alone tool as well as additional information about the methods used in PIPSA please visit our tool usage page or our theory page.

PIPSA analysis

A walkthrough demonstration can be found here. A PIPSA analysis allows the comparision of proteins with respect to their electrostatic properties. Currently two different entry points exist for starting an analysis using webPIPSA (the webserver implementation of PIPSA).
  1. Starting with a set of PDB entry codes or PDB protein structure files
  2. Starting with a SWISSPROT accession code
The latter workflow is part of SYCAMORE, a systems biology workbench and described there in more detail.

webPIPSA user guide for an analysis starting with PDB structures

Prerequisites

The standard PIPSA analysis requires protein structures as input data. These structures need to be of a similar fold and may optionally be superimposed before upload.

A variant of the PIPSA workflow can be launched using a SWISSPROT accession code as input. The related SWISSPROT entry needs to be an enzyme and annotated with an EC number. Since for this workflow, a protein structural modelling is performed using MODELLER, a license key for MODELLER is required. This workflow may be used to assist kinetic parameter estimation by qPIPSA and is also integrated in SYCAMORE (SYstems biology's Computational Analysis and MOdeling Research Environment). Additional information on the qPIPSA workflow can be found in the respective user guide.

User guide for the standard PIPSA analysis

For the PIPSA analysis a set of proteins will be compared based on their electrostatic properties.

How do I launch an analysis?

Calculation and results

Used tools

This webserver implements a workflow utilizing several commandline tools (not all may be used in a single workflow). Here we acknowledge the use of the following scientific tools:

ToolUsage in webPIPSAReferenceDetails (eg. input parameters etc).
BL2SEQUsed within the structural alignment protocol.Altschul, S.F., Gish, W., Miller, W., Myers, E.W. and Lipman, D.J. (1990) Basic local alignment search tool. J Mol Biol, 215, 403-410.
WHATIFUsed for adding polar hydrogen.Vriend, G. (1990) WHAT IF: A molecular modeling and drug design program. J. Mol. Graph., 8, 52-56.
UHBDOne option for calculating electrostatic potentials.Madura, J.D., Briggs, J.M., Wade, R.C., Davis, M.E., Luty, B.A., Ilin, A., Antosiewicz, J., Gilson, M.K., Bagheri, B., Scott, L.R. et al. (1995) Electrostatics and diffusion of molecules in solution: Simulations with the University of Houston Brownian dynamics program. Comp. Phys. Comm., 1995.UHBD template input file
PDB2PQRPreparation of APBS runs.Dolinsky TJ, Nielsen JE, McCammon JA, Baker NA. PDB2PQR: an automated pipeline for the setup, execution, and analysis of Poisson-Boltzmann electrostatics calculations. Nucleic Acids Research, 32, W665-W667 (2004).
APBSOne option for calculating electrostatic potentials.Baker, N.A., Sept, D., Joseph, S., Holst, M.J. and McCammon, J.A. (2001) Electrostatics of nanosystems: application to microtubules and the ribosome. Proc. Natl. Acad. Sci. USA, 98, 10037-10041.APBS template input file
TCOFFEEUsed for comparative modelling.3DCoffee: Combining Protein Sequences and Structures within Multiple Sequence Alignments. O. O'Sullivan, K Suhre, C. Abergel, D.G. Higgins, C. Notredame. Journal of Molecular Biology,Vol 340, pp385-395,2004.
CLUSTALWUsed for comparative modelling.Chenna, R. et al. (2003): Multiple sequence alignment with the Clustal series of programs. In: Nucleic Acid Research. Bd. 31, S. 3497-3500.
MODELLERUsed for generating protein structural models from protein sequences and structural templates.Sali, A. and Blundell, T.L. (1993) Comparitive protein modelling by satisfaction of spatial restraints. J. Mol. Biol., 234, 779-815.
PIPSAComparison of electrostatic potentials.Blomberg, N., Gabdoulline, R.R., Nilges, M. and Wade, R.C. (1999) Classification of protein sequences by homology modeling and quantitative analysis of electrostatic similarity. Proteins, 37, 379-387.
PHYLIPProduces a tree view available in the result directory.Felsenstein, J. 1989. PHYLIP - Phylogeny Inference Package (Version 3.2). Cladistics 5: 164-166.
R-PROJECTClustering of the output and drawing of heat map.Ihaka, R. and Gentleman, R. (1996) R: A language for data analysis and graphics. Journal of Computational and Graphical Statistics, 5, 299-314.
Astex-Viewer(TM)Used for visualization of structures.Hartshorn, M.J. (2002) AstexViewer (TM): a visualisation aid for structure-based drug design. Journal of Computer-aided Molecular Design, 16, 871-881.