Bioinformatics Tools
The following software and web-based bioinformatics tools are
used in various aspects of the PMT project. TOPO2 is used to create
the transmembrane protein topology images and the rest of the listed
resources are used in modeling efforts.
MODELLER, a program for comparative protein structure modeling by
satisfaction of spatial restraints
MODELLER is a computer program for comparative protein structure modeling (http://salilab.org/modeller) (A. Sali,
T.L. Blundell. "Comparative protein modelling by satisfaction of spatial restraints." J. Mol. Biol. 234, 779-815,
1993). In the simplest case, the input is an alignment of a sequence to be modeled with the template structures,
the atomic coordinates of the templates, and a short script file. MODELLER then automatically calculates a model
containing all non-hydrogen atoms, without any user intervention and within minutes on a Pentium processor.
MODWEB, a web server for automated comparative modeling that relies
on MODELLER
MODWEB is a web server for automated comparative protein structure modeling (http://salilab.org/modweb) (N. Eswar,
B. John, N. Mirkovic, A. Fiser, V.A. Ilyin, U. Pieper, A.C. Stuart, M.A. Marti-Renom, M.S. Madhusudhan, B.
Yerkovich, A. Sali. "Tools for comparative protein structure modeling and analysis." Nucl. Acids Res. 31,
3375-3380, 2003). MODWEB accepts one or many sequences in the FASTA format and calculates models for them based on
the best available template structures from the Protein Data Bank (PDB). Alternately, MODWEB also accepts a
protein structure as an input and calculates models for all its identifiable sequence homologs in the
non-redundant SwissProt protein sequence database.
MODLOOP, a web server for automated loop modeling that relies on
MODELLER
MODLOOP is a web server for explicit modeling of loops in protein structures (http://salilab.org/modloop) (A.
Fiser and A. Sali, "ModLoop: Automated modeling of loops in protein structures." Bioinformatics, in press). The
server requires an input consisting of a coordinate file (PDB format), the starting and ending residue positions
of the loops, and the number of independent optimization runs in the search for the best prediction. The user can
also specify several loops to be optimized simultaneously, which is particularly useful in the case of multiple
interacting loops. The single best prediction is returned to the user by e-mail.
MOULDER, a CPU intensive protocol of MODWEB for building comparative
models based on distant known structures
MOULDER is an optional protocol available to the MODWEB web server (http://salilab.org/modweb) (B. John, A. Sali.
"Comparative protein structure modeling by iterative alignment, model building, and model assessment." Nucl. Acids
Res. 31, 3982-8992, 2003). If chosen, an iteration of target-template alignment, model building, and model
assessment replaces the default model building step by MODELLER in the standard MODPIPE protocol. Other input and
output specifications are as described for MODWEB.
MODBASE, a comprehensive database of annotated comparative models
for all sequences detectably related to a known structure
MODBASE is a comprehensive relational database of annotated comparative protein structure models (Pieper,U.,
Eswar,N., Stuart,A.C., Ilyin,V.A. and Sali,A. "MODBASE, a database of annotated comparative protein structure
models." Nucl. Acids Res. 30, 255-259, 2002). It contains several model datasets, including that for all available
protein sequences matched to at least one known protein structure (http://salilab.org/modbase). This dataset was
calculated by applying MODELLER to all sequences in the SWISSPROT database (March 2002). Currently, MODBASE
contains models for domains in 415,937 out of 733,239 (~57%) unique protein sequences found in SWISSPROT.
SNPWEB, a web server for structure-based prediction
of a functional impact of a single amino acid substitution
SNPWEB is a web server for prediction of the functional effect of a single amino acid residue substitution
(http://salilab.org/snpweb-cgi/snpweb.cgi) (N. Eswar, B. John, N. Mirkovic, A. Fiser, V.A. Ilyin, U. Pieper,
A.C. Stuart, M.A. Marti-Renom, M.S. Madhusudhan, B. Yerkovich, A. Sali. "Tools for comparative protein
structure modeling and analysis." Nucleic Acids Research 31, 3375-3380, 2003). The server takes as input the
specifications of the wild-type protein structure and a single amino acid residue substitution. The output, in a
matter of minutes, is a prediction of whether or not the function of the mutant is impaired, as well as the
rationalization of the predicted impact in terms of several features of the wild-type and mutant structures.
TOPO2, a web based method for displaying the secondary
structure of transmembrane proteins.
TOPO2 is a transmembrane protein display tool that takes user provided information and creates a 2D image of the
protein. TOPO2 is a simple graphics program and does not even attempt to predict the location of the transmembrane
segments it displays. It finds glycosylation sites and cysteines on the exterior side of the membrane, if
requested to do so. It can also color code membrane bound amino acids with the following characteristics: acidic
and basic amino acids, amine groups, those containing hydroxyl groups, prolines and aromatic amino acids. Any
other amino acid of interest throughout the protein can also be color coded if its position is known. Consecutive
sequence regions or signature regions can also be colored.
