C. Sudandiradoss

Bio: C. Sudandiradoss is an academic researcher from VIT University. The author has contributed to research in topics: Docking (molecular) & Single-nucleotide polymorphism. The author has an hindex of 13, co-authored 39 publications receiving 559 citations.

Ab initio coordination chemistry for nickel chelation motifs.

Abstract: Chelation therapy is one of the most appreciated methods in the treatment of metal induced disease predisposition Coordination chemistry provides a way to understand metal association in biological structures In this work we have implemented coordination chemistry to study nickel coordination due to its high impact in industrial usage and thereby health consequences This paper reports the analysis of nickel coordination from a large dataset of nickel bound structures and sequences Coordination patterns predicted from the structures are reported in terms of donors, chelate length, coordination number, chelate geometry, structural fold and architecture The analysis revealed histidine as the most favored residue in nickel coordination The most common chelates identified were histidine based namely HHH, HDH, HEH and HH spaced at specific intervals Though a maximum coordination number of 8 was observed, the presence of a single protein donor was noted to be mandatory in nickel coordination The coordination pattern did not reveal any specific fold, nevertheless we report preferable residue spacing for specific structural architecture In contrast, the analysis of nickel binding proteins from bacterial and archeal species revealed no common coordination patterns Nickel binding sequence motifs were noted to be organism specific and protein class specific As a result we identified about 13 signatures derived from 13 classes of nickel binding proteins The specifications on nickel coordination presented in this paper will prove beneficial for developing better chelation strategies

Patterns of Somatic Mutation in Human Cancer Genomes

Abstract: AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore PL02-05 All cancers are due to abnormalities in DNA. The availability of the human genome sequence has led to the proposal that resequencing of cancer genomes will reveal the full complement of somatic mutations and hence all the cancer genes. To explore the nature of the information that will be derived from cancer genome sequencing we have sequenced the coding exons of the family of 518 protein kinases, ~1.3Mb DNA per cancer sample, in 210 cancers of diverse histological types. Despite the screen being directed toward the coding regions of a gene family that has previously been strongly implicated in oncogenesis, the results indicate that the majority of somatic mutations detected are “passengers”. There is considerable variation in the number and pattern of these mutations between individual cancers, indicating substantial diversity of processes of molecular evolution between cancers. The imprints of exogenous mutagenic exposures, mutagenic treatment regimes and DNA repair defects can all be seen in the distinctive mutational signatures of individual cancers. This systematic mutation screen and others have previously yielded a number of cancer genes that are frequently mutated in one or more cancer types and which are now anticancer drug targets (for example BRAF , PIK3CA , and EGFR ). However, detailed analyses of the data from our screen additionally suggest that there exist a large number of additional “driver” mutations which are distributed across a substantial number of genes. It therefore appears that cells may be able to utilise mutations in a large repertoire of potential cancer genes to acquire the neoplastic phenotype. However, many of these genes are employed only infrequently. These findings may have implications for future anticancer drug development.

Using SIFT and PolyPhen to Predict Loss-of-Function and Gain-of-Function Mutations

Abstract: Context: The interpretation of novel missense variants is a challenge with increasing numbers of such variants being identified and a responsibility to report the findings in the context of all available scientific evidence. Various in silico bioinformatic tools have been developed that predict the likely pathogenicity of missense variants; however, their utility within the diagnostic setting requires further investigation. Aim: The aim of our study was to test the predictive value of two of these tools, sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen), in a set of 141 missense variants (131 pathogenic, 8 benign) identified in the ABCC8, GCK, and KCNJ11 genes. Methods: Sixty-six of the mutations caused a gain of protein function, while 67 were loss-of-function mutations. The evolutionary conservation at each residue was also investigated using multiple sequence alignments from the UCSC genome browser. Results: The sensitivity of SIFT and PolyPhen was reasonably high (69% and...

In silico investigation of molecular mechanism of laminopathy caused by a point mutation (R482W) in lamin A/C protein

Abstract: Lamin A/C proteins are the major components of a thin proteinaceous filamentous meshwork, the lamina, that underlies the inner nuclear membrane. A few specific mutations in the lamin A/C gene cause a disease with remarkably different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan-type), which mainly affects adipose tissue. Lamin A/C mutant R482W is the key variant that causes FPLD. Biomolecular interaction and molecular dynamics (MD) simulation analysis were performed to understand dynamic behavior of native and mutant structures at atomic level. Mutant lamin A/C (R482W) showed more interaction with its biological partners due to its expansion of interaction surface and flexible nature of binding residues than native lamin A/C. MD simulation clearly indicates that the flexibility of interacting residues of mutant are mainly due to less involvement in formation of inter and intramolecular hydrogen bonds. Our analysis of native and Mutant lamin A/C clearly shows that the structural and functional consequences of the mutation R482W causes FPLD. Because of the pivotal role of lamin A/C in maintaining dynamics of nuclear function, these differences likely contribute to or represent novel mechanisms in laminopathy development.

Drug resistance mechanism of PncA in Mycobacterium tuberculosis

Abstract: Tuberculosis continues to be a global health threat. Pyrazinamide (PZA) is an important first-line drug in multidrug-resistant tuberculosis treatment. The emergence of strains resistant to PZA represents an important public health problem, as both first- and second-line treatment regimens include PZA. It becomes toxic to Mycobacterium tuberculosis when converted to pyrazinoic acid by the bacterial pyrazinamidase (PncA) enzyme. Resistance to PZA is caused mainly by the loss of enzyme activity by mutation, the mechanism of resistance is not completely understood. In our studies, we analysed three mutations (D8G, S104R and C138Y) of PncA which are involved in resistance towards PZA. Binding pocket analysis solvent accessibility analysis, molecular docking and interaction analysis were performed to understand the interaction behaviour of mutant enzymes with PZA. Molecular dynamics simulations were conducted to understand the three-dimensional (3D) conformational behaviour of native and mutants PncA. Our analy...