Showing papers by "R. Rajasekaran published in 2008"
TL;DR: The genetic variations that can alter the expression and function of the CFTR gene responsible for causing cystic fibrosis are analyzed using computational methods to identify potential candidates for future studies on CFTR mutations.
Abstract: Single Nucleotide Polymorphisms (SNPs) are being intensively studied to understand the biological basis of complex traits and diseases. The Genetics of human phenotype variation could be understood by knowing the functions of SNPs. In this study using computational methods, we analyzed the genetic variations that can alter the expression and function of the CFTR gene responsible candidate for causing cystic fibrosis. We applied an evolutionary perspective to screen the SNPs using a sequence homology-based SIFT tool, which suggested that 17 nsSNPs (44%) were found to be deleterious. The structure-based approach PolyPhen server suggested that 26 nsSNPS (66%) may disrupt protein function and structure. The PupaSuite tool predicted the phenotypic effect of SNPs on the structure and function of the affected protein. Structure analysis was carried out with the major mutation that occurred in the native protein coded by CFTR gene, and which is at amino acid position F508C for nsSNP with id (rs1800093). The amino acid residues in the native and mutant modeled protein were further analyzed for solvent accessibility, secondary structure and stabilizing residues to check the stability of the proteins. The SNPs were further subjected to iHAP analysis to identify htSNPs, and we report potential candidates for future studies on CFTR mutations.
55 citations
TL;DR: This work analyzed the SNPs that can alter the expression and function of transcriptional factor TP53 as a pipeline and proposed modeled structure for the mutant proteins and compared them with the native protein.
Abstract: Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans Understanding the functions of SNPs can greatly help to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging by experimental protocols To explore possible relationships between genetic mutation and phenotypic variation, different computational algorithm tools like Sorting Intolerant from Tolerant, Polymorphism Phenotyping, UTRscan, FASTSNP, and PupaSuite were used for prioritization of high-risk SNPs in coding region (exonic nonsynonymous SNPs) and noncoding regions (intronic and exonic 5' and 3'-untranslated region (UTR) SNPs) In this work, we have analyzed the SNPs that can alter the expression and function of transcriptional factor TP53 as a pipeline and for providing a guide to experimental work We identified the possible mutations and proposed modeled structure for the mutant proteins and compared them with the native protein These nsSNPs play a critical role in cancer association studies aiming to explain the disparity in cancer treatment responses as well as to improve the effectiveness of the cancer treatments Our results endorse the study with in vivo experimental protocols
51 citations
TL;DR: It is proposed that this most deleterious nsSNP with an SNPid rs28897759 is an important candidate for the cause of breast cancer by BRCA2 gene.
39 citations
TL;DR: The results clearly suggest that Ritonavir is not able to appropriately bind at the active site of each HIV-1 protease mutant due to RMSD difference of the amino acid (Asp) at the position 25 of all mutants.
36 citations
TL;DR: In this paper, the most deleterious non-synonymous SNP of ERBB2 (HER2) receptors by its stability and its binding affinity with herceptin was identified.
33 citations
TL;DR: It is proposed that, both the mutations 159 (L-->P) and 178 (G-->S) should be considered important in the chronic myeloid leukemia caused by ABL1 gene.
19 citations
TL;DR: It is proposed that the SNP with the ID rs11552822 could be the most deleterious nsSNP in CDKN2A gene, causing malignant melanoma, as it was well correlated with experimental studies carried out elsewhere.
14 citations
TL;DR: The predicted structure of the human D1 dopamine receptor is used to understand the mechanism of interactions between scorpion neurotoxins through the protein-protein docking method.
5 citations
TL;DR: The results obtained in this work will be very helpful in further enhancement of understanding the research on modeling and drug design with respect to the D2 dopamine receptor.
4 citations
TL;DR: It is proposed that the nsSNP with a SNPid of rs5030812 is an important candidate for the cause of von Hippel–Lindau syndrome via the VHL gene.
Abstract: In this work we have analyzed the genetic variation that can alter the expression and the function of the VHL gene using computational methods. Of 110 single nucleotide polymorphisms (SNPs), 33 were found to be nonsynonymous (nsSNPs) and 23 SNPs were found in untranslated regions. Of the 33 nsSNPs investigated, 36.3% were found to be deleterious by both SIFT and PolyPhen servers. An untranslated region (UTR) resource tool suggested that two SNPs in the 5′ UTR region and six SNPs in the 3′ UTR region might change the protein expression levels. It was found by both SIFT and PolyPhen servers that a mutation from histidine to arginine at position 115 of the native protein of the VHL gene was most deleterious. A structural analysis of this mutated protein and the native protein was performed and had a root mean square deviation (RMSD) of 2.78 A. Based on this work, we propose that the nsSNP with a SNPid of rs5030812 is an important candidate for the cause of von Hippel–Lindau syndrome via the VHL gene.
01 Jan 2008
TL;DR: The results obtained in this work will be very helpful in further enhancement of understanding the research on modeling and drug design with respect to the D2 dopamine receptor.
Abstract: We report the results on the computation of binding affinity, electrostatic free energies, contact free energies, secondary structures, stabilization centers and stabilizing residues of binding residues during the molecular docking of selected scorpion neurotoxins with D2 dopamine receptor. All the scorpion neurotoxins showed a good and satisfactory docking with the D2 receptor molecule except one neurotoxin 2SN3. We computed multiple alignment studies, solvent accessibility calculations, secondary structure analysis, stabilization centers and stabilizing residues before and after the docking process. Overall, we emphasize that the results obtained in this work will be very helpful in further enhancement of understanding the research on modeling and drug design with respect to the D2 dopamine receptor. 2008 Elsevier Ltd. All rights reserved.