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Jaap Heringa

Publications and source records attributed to Jaap Heringa.

8 recordsLinked to original sources
PubMed2003

Testing homology with Contact Accepted mutatiOn (CAO): a contact-based Markov model of protein evolution.

Point Accepted Mutation (PAM) is the Markov model of amino acid replacements in proteins introduced by Dayhoff and her co-workers (Dayhoff et al., 1978). The PAM matrices and other matrices based on the PAM model have been widely accepted as the standard scoring system of protein sequence similarity in protein sequence alignment tools. Here, we present Contact Accepted mutatiOn (CAO), a Markov model of protein residue contact mutations. The CAO model simulates the interchanging of structurally defined side-chain contacts, and introduces additional structural information into protein sequence alignments. Therefore, similarities between structurally conserved sequences can be detected even without apparent sequence similarity. CAO has been benchmarked on the HOMSTRAD database and a subset of the CATH database, by comparing sequence alignments with reference alignments derived from structural superposition. CAO yields scores that reflect coherently the structural quality of sequence alignments, which has implications particularly for homology modelling and threading techniques.

Amino Acid Sequence↗
PubMed2002

Protein domain identification and improved sequence similarity searching using PSI-BLAST.

Protein sequences containing more than one structural domain are problematic when used in homology searches where they can either stop an iterative database search prematurely or cause an explosion of a search to common domains. We describe a method, DOMAINATION, that infers domains and their boundaries in a query sequence from local gapped alignments generated using PSI-BLAST. Through a new technique to recognize domain insertions and permutations, DOMAINATION submits delineated domains as successive database queries in further iterative steps. Assessed over a set of 452 multidomain proteins, the method predicts structural domain boundaries with an overall accuracy of 50% and improves finding distant homologies by 14% compared with PSI-BLAST. DOMAINATION is available as a web based tool at http://mathbio.nimr.mrc.ac.uk, and the source code is available from the authors upon request.

Animals↗
PubMed2002

SnapDRAGON: a method to delineate protein structural domains from sequence data.

We describe a method to identify protein domain boundaries from sequence information alone based on the assumption that hydrophobic residues cluster together in space. SnapDRAGON is a suite of programs developed to predict domain boundaries based on the consistency observed in a set of alternative ab initio three-dimensional (3D) models generated for a given protein multiple sequence alignment. This is achieved by running a distance geometry-based folding technique in conjunction with a 3D-domain assignment algorithm. The overall accuracy of our method in predicting the number of domains for a non-redundant data set of 414 multiple alignments, representing 185 single and 231 multiple-domain proteins, is 72.4 %. Using domain linker regions observed in the tertiary structures associated with each query alignment as the standard of truth, inter-domain boundary positions are delineated with an accuracy of 63.9 % for proteins comprising continuous domains only, and 35.4 % for proteins with discontinuous domains. Overall, domain boundaries are delineated with an accuracy of 51.8 %. The prediction accuracy values are independent of the pair-wise sequence similarities within each of the alignments. These results demonstrate the capability of our method to delineate domains in protein sequences associated with a wide variety of structural domain organisation.

Algorithms↗
PubMed2002

Local weighting schemes for protein multiple sequence alignment.

This paper describes three weighting schemes for improving the accuracy of progressive multiple sequence alignment methods: (1) global profile pre-processing, to capture for each sequence information about other sequences in a profile before the actual multiple alignment takes place; (2) local pre-processing; which incorporates a new protocol to only use non-overlapping local sequence regions to construct the pre-processed profiles; and (3) local-global alignment, a weighting scheme based on the double dynamic programming (DDP) technique to softly bias global alignment to local sequence motifs. The first two schemes allow the compilation of residue-specific multiple alignment reliability indices, which can be used in an iterative fashion. The schemes have been implemented with associated iterative modes in the PRALINE multiple sequence alignment method, and have been evaluated using the BAliBASE benchmark alignment database. These tests indicate that PRALINE is a toolbox able to build alignments with very high quality. We found that local profile pre-processing raises the alignment quality by 5.5% compared to PRALINE alignments generated under default conditions. Iteration enhances the quality by a further percentage point. The implications of multiple alignment scoring functions and iteration in relation to alignment quality and benchmarking are discussed.

Amino Acid Motifs↗
PubMed2002

Parallelized multiple alignment.

UNLABELLED: Multiple sequence alignment is a frequently used technique for analyzing sequence relationships. Compilation of large alignments is computationally expensive, but processing time can be considerably reduced when the computational load is distributed over many processors. Parallel processing functionality in the form of single-instruction multiple-data (SIMD) technology was implemented into the multiple alignment program Praline by using 'message passing interface' (MPI) routines. Over the alignments tested here, the parallelized program performed up to ten times faster on 25 processors compared to the single processor version. AVAILABILITY: Example program code for parallelizing pairwise alignment loops is available from http://mathbio.nimr.mrc.ac.uk/~jkleinj/tools/mpicode. The 'message passing interface' package (MPICH) is available from http:/www.unix.mcs.anl.gov/mpi/mpich. CONTACT: jhering@nimr.mrc.ac.uk SUPPLEMENTARY INFORMATION: Praline is accessible at http://mathbio.nimr.mrc.ac.uk/praline.

Algorithms↗
PubMed2002

An analysis of protein domain linkers: their classification and role in protein folding.

Recent advances in protein engineering have come from creating multi-functional chimeric proteins containing modules from various proteins. These modules are typically joined via an oligopeptide linker, the correct design of which is crucial for the desired function of the chimeric protein. Here we analyse the properties of naturally occurring inter-domain linkers with the aim to design linkers for domain fusion. Two main types of linker were identified; helical and non-helical. Helical linkers are thought to act as rigid spacers separating two domains. Non-helical linkers are rich in prolines, which also leads to structural rigidity and isolation of the linker from the attached domains. This means that both linker types are likely to act as a scaffold to prevent unfavourable interactions between folding domains. Based on these results we have constructed a linker database intended for the rational design of linkers for domain fusion, which can be accessed via the Internet at http://mathbio.nimr.mrc.ac.uk.

Chi-Square Distribution↗
PubMed2002

A Fourier analysis of symmetry in protein structure.

The score matrix from a structure comparison program (SAP) was used to search for repeated structures using a Fourier analysis. When tested with artificial data, a simple Fourier transform of the smoothed matrix provided a clear signal of the repeat periodicity that could be used to extract the repeating units with the SAP program. The strength of the Fourier signal was calibrated against the signal from model proteins. The most useful of these was the novel random-walk approach employed to generate realistic 'fake' structures. On the basis of these it was possible to conclude that only a small proportion of protein structures have an unexpected degree of symmetry. Artificially generated 'ideal' folds provided an upper limit on the strength of signal that could be expected from a 'perfectly' repeating compact structure. Unexpectedly, some of the very regular beta-propellor folds attained the same strength but the majority of symmetric structures lay below this region. When native proteins were ranked by the power of their spectrum a wide variety of fold types were seen to score highly. In the betaalpha class, these included the globular betaalpha proteins and the more repetitive leucine-rich betaalpha folds. In the all-beta class; beta-propellors, beta-prisms and beta-helices were found as well as the more globular gamma-crystalin domains. When this ranked list was filtered to remove proteins that contained detectable internal sequence similarity (using the program REPRO), the list became exclusively composed of just globular betaalpha class proteins and in the top 50 re-ranked proteins, only a single 4-fold propellor structure remained.

Fourier Analysis↗