Prediction of RNA 3D Structure using Parallel Algorithm

RNA structures are generally organized hierarchically organized. Prediction of RNA structure is a big challenge for the researchers. Many prediction algorithms have been develop for RNA secondary structure prediction. But prediction of tertiary structure is still a big area of research. Approaches for RNA tertiary structure prediction are broadly categorized into two methods viz. de novo methods and template-based prediction method. The De novo are useful only for the small sequences of the nucleotides. For the sequences with large number of nucleotides template based modelling technique is more useful. These template based method are very common in protein structure prediction but it is not explored in RNA tertiary structure prediction. This paper presents a novel methodology for prediction of RNA tertiary structure using the bank ok known structure (template). First, the RNA secondary structure is analysed on the basis of free nucleotides available region wise which may contribute in the prediction of tertiary structure. Next similar region structure templates are searched in PDB metadata. These templates are then used to for the tertiary structure. As all the templates stored in PDB are predicted structures with minimum negative energy, the resultant tertiary structure is also consequently has minimum negative energy. The proposed method is able to predict even large ribosomal RNA structures. The experimental results have shown for the predicted structures on the basis of percentage similarity as well as time required for prediction

Predikce terciární struktury RNA na základě předlohy

Práca sa zaoberá návrhom, implementáciou a testovaním nového algoritmu homológnej predikcie terciárnej RNA štruktúry, teda predikcie za pomoci podobnej RNA štruktúry ako vzoru. Zameriava sa na možnosť predikcie dlhých RNA štruktúr v rozumnom čase a dobrej presnosti. Algoritmus je založený na skopírovaní konzervovaných častí štruktúry vzoru a následnom dopredikovaní nekonzervovaných úsekov existujúcim algoritmom typu ab initio. Práca je rozdelená na štyri kapitoly. Prvá obsahuje základné informácie o RNA a o jej význame, druhá popisuje spôsoby predikcie RNA a súčasne dostupné metódy predikcie, v tretej je predstavený algoritmus a vo štvrtej sú vyhodnotené výsledky vyvinutého algoritmu.The thesis deals with proposal, implementation and testing of a new algorithm for homologous tertiary RNA structure prediction, which means using a structure similar to the template. It focuses on the possibility of large RNA structures prediction in reasonable time and precision. The algorithm is based on copying conserved parts of template structure into the target structure. The unconserved parts are then predicted by an existing ab initio algorithm. The thesis is divided into four chapters. The first one contains basic information about RNA and its importance. The second one describes different ways of RNA prediction and it contains an overwiev of currently available prediction methods. The third one describes the invented algorithm and the fourth one presents achieved results.Department of Software EngineeringKatedra softwarového inženýrstvíMatematicko-fyzikální fakultaFaculty of Mathematics and Physic

Molecular modelling and Function Prediction of hABH7, human homologue of _E. coli_ ALKB7

Human homologues of ALKB protein have shown the prime role in DNA damaging drugs, used for cancer therapy. Little is known about structure and function of hABH7, one of the members of this superfamily. Therefore, in the present study we intend to predict its structure and function using various bioinformatics tools. Modeling was done with modeller 9v7 to predict the 3D structure of the hABH7 protein. The tertiary structure model of hABH7, ALKBH7.B99990002.pdb was predicted and evaluated. Validation results showed 97.8% residues in favored and additional allowed regions of Ramachandran plots. Ligand binding residues prediction showed four ligand clusters, having 25 ligands in cluster 1. Importantly, presence of a Phe120-Gly121-Gly122 conserved pattern in the functional domain was detected. In the predicted structural model of hABH7, amino acid residues, Arginine at 57, 58, 59 and 60 along with tyrosine at 61 were predicted in RNA binding sites of the model. The predicted and validated model of human homologue hABH7 resulting from this study may unveil the mechanism of DNA damage repair in humans and accelerate the research on designing appropriate inhibitors aiding in chemotherapy and cancer related diseases

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

Structure and function prediction of human homologue hABH5 of _E. coli_ ALKB5 using in silico approach

Newly discovered human homologues of ALKB protein have shown the activity of DNA damaging drugs, used for cancer therapy. Little is known about the structure and function of hABH5, one of the members of this superfamily. Therefore, in the present study we intend to predict its structure and function using various bioinformatics tools. Modeling was done with modeler 9v7 to predict the 3D structure of the hABH5 protein. 3-D model of hABH5, ALKBH5.B99990005.pdb was predicted and evaluated. Validation results showed 96.8% residues in favor and an additional allowed region of the Ramachandran plot. Ligand binding residues prediction showed four ligand clusters, having 25 ligands in cluster 1. Importantly, conserved pattern of Pro158-X-Asp160-Xn-His266 in the functional domain was detected. DNA and RNA binding sites were also predicted in the model. The predicted and validated model of human homologue hABH5 resulting from this study may unveil the mechanism of DNA damage repair in humans and accelerate research on designing appropriate inhibitors, aiding in chemotherapy and cancer related diseases

Structure and function prediction of human homologue hABH5 of _E. coli_ ALKB5 using in silico approach

Newly discovered human homologues of ALKB protein have shown the activity of DNA damaging drugs, used for cancer therapy. Little is known about the structure and function of hABH5, one of the members of this superfamily. Therefore, in the present study we intend to predict its structure and function using various bioinformatics tools. Modeling was done with modeler 9v7 to predict the 3D structure of the hABH5 protein. 3-D model of hABH5, ALKBH5.B99990005.pdb was predicted and evaluated. Validation results showed 96.8% residues in favor and an additional allowed region of the Ramachandran plot. Ligand binding residues prediction showed four ligand clusters, having 25 ligands in cluster 1. Importantly, conserved pattern of Pro158-X-Asp160-Xn-His266 in the functional domain was detected. DNA and RNA binding sites were also predicted in the model. The predicted and validated model of human homologue hABH5 resulting from this study may unveil the mechanism of DNA damage repair in humans and accelerate research on designing appropriate inhibitors, aiding in chemotherapy and cancer related diseases