Biomedical subjects

Venkatarajan Subramanian Mathura

Publications and source records attributed to Venkatarajan Subramanian Mathura.

4 recordsLinked to original sources

PubMed2005

Identification of critical heterodimer protein interface parameters by multi-dimensional scaling in euclidian space.

Protein subunit dimers are either homodimers (consisting of identical polypeptides) or heterodimers (consisting of different polypeptides). Protein dimers are involved in several cellular processes and an understanding of their molecular principle in complexations (subunit-subunit interaction) is essential. This is generally studied using 3D structures of homodimers and heterodimers determined by X-ray crystallography. However, the current knowledge on subunit interaction is limited due to lack of sufficient 3D dimer structures. It is our interest to study heterodimers using 3D structures to identify interaction parameters that would help in the development of a model to predict heterodimer interaction sites just from protein sequences. The efficiency of such models depends on the weighted contribution of numerous parameters characterizing heterodimer interfaces. Therefore, we studied the salient features of 111 interface parameters in 65 heterodimer structures. In this study, we applied multi-dimensional scaling for dimensionality reduction on these parameters to select the most critical ones that best characterize heterodimer interfaces. The significance of these parameters in subunit interaction is discussed.

Computational Biology↗

PubMed2004

A report on single exon genes (SEG) in eukaryotes.

Single exon genes (SEG) are archetypical of prokaryotes. Hence, their presence in intron-rich, multi-cellular eukaryotic genomes is perplexing. Consequently, a study on SEG origin and evolution is important. Towards this goal, we took the first initiative of identifying and counting SEG in nine completely sequenced eukaryotic organisms--four of which are unicellular (E. cuniculi, S. cerevisiae, S. pombe, P. falciparum) and five of which are multi-cellular (C. elegans, A. thaliana, D. melanogaster, M. musculus, H. sapiens). This exercise enabled us to compare their proportion in unicellular and multi-cellular genomes. The comparison suggests that the SEG fraction decreases with gene count (r = -0.80) and increases with gene density (r = 0.88) in these genomes. We also examined the distribution patterns of their protein lengths in different genomes.

Animals↗

PubMed2003

A novel MHCp binding prediction model.

Many statistical and molecular mechanics models have been developed and tested for major histocompatibility complex peptide (MHCp) binding predictions during the last decade. The statistical model prediction using pooled peptide sequence data and three-dimensional modeling prediction by molecular mechanics calculations have been assessed for efficiency and human leukocyte antigen diversity coverage. We describe a novel predictive model using information gleaned from 29 human MHCp crystal structures. The validation for the new model is performed using four different sets of data: (1) MHCp crystal structures, (2) peptides with known IC(50) binding values, (3) peptides tested positive by tetramer staining, (4) peptides with known binding information at the MHCBN database. The model produces high prediction efficiencies (average 60 %) with good sensitivity (approximately 50%-73%) and specificity (52%-58%) values. The average positive predictive value of the model is 89%, while the average negative predictive value is only 18%. The efficiency is very high in predicting binders and very low in predicting nonbinders. This model is superior to many existing methods because of its potential application to any given MHC allele whose sequence is clearly defined.

Amino Acid Sequence↗

PubMed2002

Types of inter-atomic interactions at the MHC-peptide interface: identifying commonality from accumulated data.

BACKGROUND: Quantitative information on the types of inter-atomic interactions at the MHC-peptide interface will provide insights to backbone/sidechain atom preference during binding. Qualitative descriptions of such interactions in each complex have been documented by protein crystallographers. However, no comprehensive report is available to account for the common types of inter-atomic interactions in a set of MHC-peptide complexes characterized by variation in MHC allele and peptide sequence. The available x-ray crystallography data for these complexes in the Protein Databank (PDB) provides an opportunity to identify the prevalent types of such interactions at the binding interface. RESULTS: We calculated the percentage distributions of four types of interactions at varying inter-atomic distances. The mean percentage distribution for these interactions and their standard deviation about the mean distribution is presented. The prevalence of SS and SB interactions at the MHC-peptide interface is shown in this study. SB is clearly dominant at an inter-atomic distance of 3A. CONCLUSION: The prevalently dominant SB interactions at the interface suggest the importance of peptide backbone conformation during MHC-peptide binding. Currently, available algorithms are developed for protein sidechain prediction upon fixed backbone template. This study shows the preference of backbone atoms in MHC-peptide binding and hence emphasizes the need for accurate peptide backbone prediction in quantitative MHC-peptide binding calculations.

Binding Sites↗