Biomedical subjects

Kellathur N Srinivasan

Publications and source records attributed to Kellathur N Srinivasan.

6 recordsLinked to original sources

PubMed2006

SCORPION2: a database for structure-function analysis of scorpion toxins.

Scorpion toxins are important experimental tools for characterization of vast array of ion channels and serve as scaffolds for drug design. General public database entries contain limited annotation whereby rich structure-function information from mutation studies is typically not available. SCORPION2 contains more than 800 records of native and mutant toxin sequences enriched with binding affinity and toxicity information, 624 three-dimensional structures and some 500 references. SCORPION2 has a set of search and prediction tools that allow users to extract and perform specific queries: text searches of scorpion toxin records, sequence similarity search, extraction of sequences, visualization of scorpion toxin structures, analysis of toxic activity, and functional annotation of previously uncharacterized scorpion toxins. The SCORPION2 database is available at http://sdmc.i2r.a-star.edu.sg/scorpion/.

Animals↗

PubMed2006

PREDNOD, a prediction server for peptide binding to the H-2g7 haplotype of the non-obese diabetic mouse.

The non-obese diabetic (NOD) mouse is a widely used animal model for study of autoimmune diseases, in particular human type 1 diabetes mellitus (T1DM). Identification of the subset of peptides that bind MHC molecules comprising the H-2g7 haplotype of NOD mouse and thereby representing potential NOD T-cell epitopes is important for research into the pathogenesis and immunotherapy of T1DM. The H-2g7 haplotype comprises the MHC class-I molecules Kd and Db and a single class-II molecule I-Ag7. We have developed a prediction system, PREDNOD, for accurate identification of peptides that bind the MHC molecules constituting the H-2g7 haplotype. PREDNOD is accessible at http://antigen.i2r.a-star.edu.sg/Ag7.

Algorithms↗

PubMed2005

MULTIPRED: a computational system for prediction of promiscuous HLA binding peptides.

MULTIPRED is a web-based computational system for the prediction of peptide binding to multiple molecules (proteins) belonging to human leukocyte antigens (HLA) class I A2, A3 and class II DR supertypes. It uses hidden Markov models and artificial neural network methods as predictive engines. A novel data representation method enables MULTIPRED to predict peptides that promiscuously bind multiple HLA alleles within one HLA supertype. Extensive testing was performed for validation of the prediction models. Testing results show that MULTIPRED is both sensitive and specific and it has good predictive ability (area under the receiver operating characteristic curve A(ROC) > 0.80). MULTIPRED can be used for the mapping of promiscuous T-cell epitopes as well as the regions of high concentration of these targets--termed T-cell epitope hotspots. MULTIPRED is available at http://antigen.i2r.a-star.edu.sg/multipred/.

Computational Biology↗

PubMed2005

PREDBALB/c: a system for the prediction of peptide binding to H2d molecules, a haplotype of the BALB/c mouse.

PRED(BALB/c) is a computational system that predicts peptides binding to the major histocompatibility complex-2 (H2(d)) of the BALB/c mouse, an important laboratory model organism. The predictions include the complete set of H2(d) class I (H2-K(d), H2-L(d) and H2-D(d)) and class II (I-E(d) and I-A(d)) molecules. The prediction system utilizes quantitative matrices, which were rigorously validated using experimentally determined binders and non-binders and also by in vivo studies using viral proteins. The prediction performance of PRED(BALB/c) is of very high accuracy. To our knowledge, this is the first online server for the prediction of peptides binding to a complete set of major histocompatibility complex molecules in a model organism (H2(d) haplotype). PRED(BALB/c) is available at http://antigen.i2r.a-star.edu.sg/predBalbc/.

Animals↗

PubMed2005

Neural models for predicting viral vaccine targets.

We applied artificial neural networks (ANN) for the prediction of targets of immune responses that are useful for study of vaccine formulations against viral infections. Using a novel data representation, we developed a system termed MULTIPRED that can predict peptide binding to multiple related human leukocyte antigens (HLA). This implementation showed high accuracy in the prediction of the promiscuous peptides that bind to five HLA-A2 allelic variants. MULTIPRED is useful for the identification of peptides that bind multiple HLA-A2 variants as a group. By implementing ANN as a classification engine, we enabled both the prediction of peptides binding to multiple individual HLA-A2 molecules and the prediction of promiscuous binders using a single model. The ANN MULTIPRED predicts peptide binding to HLA-A*0205 with excellent accuracy (area under the receiver operating characteristic curve--AROC>0.90), and to HLA-A*0201, HLA-A*0204 and HLA-A*0206 with high accuracy (AROC>0.85). Antigenic regions with high density of binders ("antigenic hot-spots") represent best targets for vaccine design. MULTIPRED not only predicts individual 9-mer binders but also predicts antigenic hot spots. Two HLA-A2 hot-spots in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) membrane protein were predicted by using MULTIPRED.

Algorithms↗

PubMed2002

kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity.

An important and exciting challenge in the postgenomic era is to understand the functions of newly discovered proteins based on their structures. The main thrust is to find the common structural motifs that contribute to specific functions. Using this premise, here we report the purification, solution NMR, and functional characterization of a novel class of weak potassium channel toxins from the venom of the scorpion Heterometrus fulvipes. These toxins, kappa-hefutoxin1 and kappa-hefutoxin2, exhibit no homology to any known toxins. NMR studies indicate that kappa-hefutoxin1 adopts a unique three-dimensional fold of two parallel helices linked by two disulfide bridges without any beta-sheets. Based on the presence of the functional diad (Tyr(5)/Lys(19)) at a distance (6.0 +/- 1.0 A) comparable with other potassium channel toxins, we hypothesized its function as a potassium channel toxin. kappa-Hefutoxin 1 not only blocks the voltage-gated K(+)-channels, Kv1.3 and Kv1.2, but also slows the activation kinetics of Kv1.3 currents, a novel feature of kappa-hefutoxin 1, unlike other scorpion toxins, which are considered solely pore blockers. Alanine mutants (Y5A, K19A, and Y5A/K19A) failed to block the channels, indicating the importance of the functional diad.

Amino Acid Sequence↗