International Journal of Computational Bioinformatics and In Silico Modeling
ABSTRACT: Ambystoma mexicanum an obligate paedomorphic species has large number of substitution in the interaction in Alpha and Beta chain residues of its hemoglobin that enable it to survive in hypoxic and lower oxygen pressure condition. To understand the mechanism of respiration in A. mexicanum we need to understand the three dimensional structure of its hemoglobin. In this study, we have built a three dimensional homology model of hemoglobin A (HbA) from A. mexicanum using bovine HbA as template. MODELLER was used to create three dimensional patterns and was evaluated with ProSA and PROCHECK. This study is about the analysis of effects of inter-subunit contacts on oxygen affinity of the hemoglobin. The effect of the following pairs of inter-subunit contacts on the oxygen affinity of the hemoglobin have been studied i.e. α99 and β101, α34 and β125, α38 and β99 and β97, α119and β55, α35 and β128, and α103 and β112. It has been predicted from the loss of interactions between these pairs of residues that A. mexicanum HbA might be able to tolerate hypoxic conditions and have greater oxygen affinity.
KeyWords: Ambystoma mexicanum, oxygen affinity, hypoxic state, inter sub unit contacts.
How to cite: Abid Ali et. al. Int J Comput Bioinfo In Silico Model. 3(3) 2014: 369-373
ABSTRACT: The phylogenetic analysis indicated that Tamil Nadu isolates of Marek’s disease viruses formed a cluster with very virulent MDV strains. Multiple sequence alignment of amino acid sequences of Meq protein showed variation among the Tamil Nadu isolates at position 71st (threonine instead of isoleucine) and was found to be important for transactivation of the Meq promoter. Due to the non-availability of Meq protein structure in protein databases, In silico modeling of the Meq protein of Tamil Nadu strain , RB-1B (vvMEQ), 648A (vv+MEQ) strains was successfully carried out using the Modeller9.10 software. The generated models were evaluated using PROSA, PROCHECK, PROMOTIF. Ramachandran plot analysis, z-score statistical analysis and energy distribution of protein structure models were enumerated. The amino acid variations in modeled structures as motif may be useful to evaluate epitope vaccines to protect oncogenic MDV.
KeyWords: Marek’s disease virus, meq gene, phylogenetic analysis, multiple sequence alignment, protein structure modeling, epitope prediction
How to cite: G. Sathish et. al. Int J Comput Bioinfo In Silico Model. 3(3) 2014: 374-380
ABSTRACT: TRPM1 (Transient receptor potential melastatin 1) was identified in 1998 as a protein down-regulated in highly metastatic melanoma cells. In Melanocytes, TRPM1 expression is necessary for the function of endogenous nonselective cation channels with constitutive activity, while experimentally down-regulating TRPM1 expression diminished these currents. The structural mechanism of TRPM1 is still unknown, so, we modeled the three dimensional structure to predict the structural mechanism of human TRPM1. MOE was utilized to generate three dimensional structure of the human TRPM1 candidate gene. The quality of the constructed model was checked by Rampage and ERRAT. Molecular-dynamics simulations were carried out to characterize the dynamic behavior of the protein. Our results showed an open motion of the protein in water solvent. The generated model will help in understanding the mechanism of TRPM1 protein and will provide an incentive for new studies.
KeyWords: TRPM1, Modeling, validation, MD-simulation, Phylogenetic analysis
How to cite: A Wadood et. al. Int J Comput Bioinfo In Silico Model. 3(3) 2014: 381-387
ABSTRACT: Next-generation sequencing (NGS) technology becomes the premier tool in genetic and genomic analysis by offering high-throughput sequencing.The identification of causer variant of genetic disease became a great challenge. Various in silico bioinformatics tools have been used to predict deleterious effect of mutation associated with hearing impairment among Sudanese patients. Our aim was to explore whether other genes, than those reported single nucleotide polymorphisms (SNPs), associated with deafness are found among Sudanese patients using multiple algorithms tools. NGS data of two Sudanese families were analyzed in silico. The potentially functional nonsynonymous single nucleotide polymorphisms (nsSNPs) and their effect on protein was predicted by Polymorphism Phenotype (PolyPhen) and Sort Intolerant from Tolerant (SIFT) softwares, respectively. Protein stability change was calculated using I-Mutant 2.0. University of California, San Francisco (UCSF) chimera software was used to compare between the 3D structure of wild and mutant type of proteins. Our analysis showed deleterious nsSNP's in GJB3 and GJB4 genes ranging from 0.00-0.05 (SIFT), >1.50 (Polyphen) and decrease protein activity (I-mutant), and accordingly the candidate genes were selected as a causative variant of hearing impairment in two Sudanese families. In conclusion, NGS provides data to facilitate the discovery of variants associated with hearing impairment. The accuracy of deleterious nsSNPs predicted can be increased by combining different computational methods as SIFT, Polyphen2 and I-Mutant 2.0.
KeyWords: Next generation sequencing; nonsynonymous single nucleotide polymorphisms; GJB3; GJB4; deafness
How to cite: Mohamed A. Salih et. al. Int J Comput Bioinfo In Silico Model. 3(3) 2014: 388-392
ABSTRACT: This paper presents 3D computer model of the hip joint cartilage in the ANSYS program. Model is made on the basis of anatomy and collected data on the material constants of bone and cartilage components. Analysis and comparison of biochemical model, viscoelastic and molecular mixed - aggregation serves to facilitate the creation of the next model of reality, which could be used in the design of joint prostheses. The correctness of the model was tested in a series of simulations for three different cases in which distinguished 15 variants of the "stickiness - order". The results for one of them is presented in the form of graphs.
KeyWords: hip, articular cartilage, a computer model
How to cite: Magdalena Karczewska. Int J Comput Bioinfo In Silico Model. 3(3) 2014: 393-397
ABSTRACT: Nipah virus is a zoonotic and negative sense single stranded RNA paramyxovirus which is classified in the genus Henipavirus, under the family of Paramyxoviridae. The Center of Disease Control has declared it as a biosafety level 4 agent due to which it has attracted the interest of many researchers. The present work is aimed towards the characterization of Nipah virus proteins, in order to identify the reason behind virus’ pathogenicity. The nipah virus structural proteins were characterized via various computational tools like CLC protein workbench, protparam, SOPMA, CysRec tool and SOSUI Server. Primary structure analysis shows that most of the proteins in nipah virus are hydrophobic in nature due to the presence of high content of non-polar residues. Secondary structure analysis shows that nipah virus proteins have predominant and high coil structural content which may be due to the rich content of more flexible glycine and hydrophobic proline amino acids. The nipah viral structural proteins were further modelled using Prime application of Schrodinger suit which was further validated through Ramachandran plot and molecular dynamics simulation. The sequence analysis can be further used for the designing of a potent antiviral drug against the virus, thereby aiding knowledge in the field of research.
KeyWords: CLC protein workbench, ExPASy, Protparam, CysRec, SOPMA, Nipah virus
How to cite: Dipika Rungta and Koel Mukherjee. Int J Comput Bioinfo In Silico Model. 3(3) 2014: 398-406
ABSTRACT: The FSSP (Fold Classification based on Structure-Structure alignment of Proteins) is based on a structural alignment of all pairwise combinations of the proteins in DALI program. PDB has a number of redundant structures of proteins whose sequences and structures are 30% or more identical. A set of representative structures within PDB without these redundant entries was first produced by aligning all of the PDB structures with DALI. Thus each protein in the subset was then subdivided into individual domains. These domains were then aligned structurally with DALI to identify common folds. Again redundant folds were eliminated, after that a set of representative folds were chosen. Therefore there is a cluster of folds that corresponds to every representative fold type that are of the similar approximate structure. Thus the domains that have already a given cluster of folds are structurally connected, and therefore the cluster is drawn by structural alignments of these domains. Thus, fold clusters could also be organized in a hierarchical fashion with folds drawn by the most low-scoring alignments at the top of the hierarchy.
KeyWords: FSSP, SCOP, DALI, CATH, MMDB, α-Helices, β-sheets
How to cite: Manish Kumar and Ajay Prakash. Int J Comput Bioinfo In Silico Model. 3(3) 2014: 407-411