Biomedical subjects

Eckart Bindewald

Publications and source records attributed to Eckart Bindewald.

7 recordsLinked to original sources

PubMed2006

CorreLogo: an online server for 3D sequence logos of RNA and DNA alignments.

We present an online server that generates a 3D representation of properties of user-submitted RNA or DNA alignments. The visualized properties are information of single alignment columns, mutual information of two alignment positions as well as the position-specific fraction of gaps. The nucleotide composition of both single columns and column pairs is visualized with the help of color-coded 3D bars labeled with letters. The server generates both VRML and JVX output that can be viewed with a VRML viewer or the JavaView applet, respectively. We show that combining these different features of an alignment into one 3D representation is helpful in identifying correlations between bases and potential RNA and DNA base pairs. Significant known correlations between the tRNA 3' anticodon cardinal nucleotide and the extended anticodon were observed, as were correlations within the amino acid acceptor stem and between the cardinal nucleotide and the acceptor stem. The online server can be accessed using the URL http://correlogo.abcc.ncifcrf.gov.

Computer Graphics↗

PubMed2006

RNA secondary structure prediction from sequence alignments using a network of k-nearest neighbor classifiers.

We present a machine learning method (a hierarchical network of k-nearest neighbor classifiers) that uses an RNA sequence alignment in order to predict a consensus RNA secondary structure. The input to the network is the mutual information, the fraction of complementary nucleotides, and a novel consensus RNAfold secondary structure prediction of a pair of alignment columns and its nearest neighbors. Given this input, the network computes a prediction as to whether a particular pair of alignment columns corresponds to a base pair. By using a comprehensive test set of 49 RFAM alignments, the program KNetFold achieves an average Matthews correlation coefficient of 0.81. This is a significant improvement compared with the secondary structure prediction methods PFOLD and RNAalifold. By using the example of archaeal RNase P, we show that the program can also predict pseudoknot interactions.

Algorithms↗

PubMed2005

Structural polymorphism of the HIV-1 leader region explored by computational methods.

Experimental studies revealed that the elements of the human immunodeficiency virus type 1 (HIV-1) 5'-untranslated leader region (5'-UTR) can fold in vitro into two alternative conformations, branched (BMH) and 'linearized' (LDI) and switch between them to achieve different functionality. In this study we computationally explored in detail, with our massively parallel genetic algorithm (MPGAfold), the propensity of 13 HIV-1 5'-UTRs to fold into the BMH and the LDI conformation types. Besides the BMH conformations these results predict the existence of two functionally equivalent types of LDI conformations. One is similar to what has been shown in vitro to exist in HIV-1 LAI, the other is a novel conformation exemplified by HIV-1 MAL long-distance interactions. These novel MPGAfold results are further corroborated by a consensus probability matrix algorithm applied to a set of 155 HIV-1 sequences. We also have determined in detail the impact of various strain mutations, domain sizes and folds of elongating sequences simulating folding during transcription on HIV-1 RNA secondary structure folding dynamics.

5' Untranslated Regions↗

PubMed2005

A scoring function for docking ligands to low-resolution protein structures.

We present a docking method that uses a scoring function for protein-ligand docking that is designed to maximize the docking success rate for low-resolution protein structures. We find that the resulting scoring function parameters are very different depending on whether they were optimized for high- or low-resolution protein structures. We show that this docking method can be successfully applied to predict the ligand-binding site of low-resolution structures. For a set of 25 protein-ligand complexes, in 76% of the cases, more than 50% of ligand-contacting residues are correctly predicted (using receptor crystal structures where the binding site is unspecified). Using decoys of the receptor structures having a 4 A RMSD from the native structure, for the same set of complexes, in 72% of the cases, we obtain at least one correctly predicted ligand-contacting residue. Furthermore, using an 81-protein-ligand set described by Jain, in 76 (93.8%) cases, the algorithm correctly predicts more than 50% of the ligand-contacting residues when native protein structures are used. Using 3 A RMSD from native decoys, in all but two cases (97.5%), the algorithm predicts at least one ligand-binding residue correctly. Finally, compared to the previously published Dolores method, for 298 protein-ligand pairs, the number of cases in which at least half of the specific contacts are correctly predicted is more than four times greater.

Algorithms↗

PubMed2004

The SSEA server for protein secondary structure alignment.

SUMMARY: We present a web server that computes alignments of protein secondary structures. The server supports both performing pairwise alignments and searching a secondary structure against a library of domain folds. It can calculate global and local secondary structure element alignments. A combination of local and global alignment steps can be used to search for domains inside the query sequence or help in the discrimination of novel folds. Both the SCOP and PDB fold libraries, clustered at 95 and 40% sequence identity, are available for alignment. AVAILABILITY: The web server interface is freely accessible to academic users at http://protein.cribi.unipd.it/ssea/. The executable version and benchmarking data are available from the same web page.

Algorithms↗

PubMed2003

MANIFOLD: protein fold recognition based on secondary structure, sequence similarity and enzyme classification.

We present a protein fold recognition method, MANIFOLD, which uses the similarity between target and template proteins in predicted secondary structure, sequence and enzyme code to predict the fold of the target protein. We developed a non-linear ranking scheme in order to combine the scores of the three different similarity measures used. For a difficult test set of proteins with very little sequence similarity, the program predicts the fold class correctly in 34% of cases. This is an over twofold increase in accuracy compared with sequence-based methods such as PSI-BLAST or GenTHREADER, which score 13-14% correct first hits for the same test set. The functional similarity term increases the prediction accuracy by up to 3% compared with using the combination of secondary structure similarity and PSI-BLAST alone. We argue that using functional and secondary structure information can increase the fold recognition beyond sequence similarity.

Algorithms↗

PubMed2002

A divide and conquer approach to fast loop modeling.

We describe a fast ab initio method for modeling local segments in protein structures. The algorithm is based on a divide and conquer approach and uses a database of precalculated look-up tables, which represent a large set of possible conformations for loop segments of variable length. The target loop is recursively decomposed until the resulting conformations are small enough to be compiled analytically. The algorithm, which is not restricted to any specific loop length, generates a ranked set of loop conformations in 20-180 s on a desktop PC. The prediction quality is evaluated in terms of global RMSD. Depending on loop length the top prediction varies between 1.06 A RMSD for three-residue loops and 3.72 A RMSD for eight-residue loops. Due to its speed the method may also be useful to generate alternative starting conformations for complex simulations.

Algorithms↗