Detecting DNA-binding helix–turn–helix structural motifs using sequence and structure information

In this work, we analyse the potential for using structural knowledge to improve the detection of the DNA-binding helix–turn–helix (HTH) motif from sequence. Starting from a set of DNA-binding protein structures that include a functional HTH motif and have no apparent sequence similarity to each other, two different libraries of hidden Markov models (HMMs) were built. One library included sequence models of whole DNA-binding domains, which incorporate the HTH motif, the second library included shorter models of ‘partial’ domains, representing only the fraction of the domain that corresponds to the functionally relevant HTH motif itself. The libraries were scanned against a dataset of protein sequences, some containing the HTH motifs, others not. HMM predictions were compared with the results obtained from a previously published structure-based method and subsequently combined with it. The combined method proved more effective than either of the single-featured approaches, showing that information carried by motif sequences and motif structures are to some extent complementary and can successfully be used together for the detection of DNA-binding HTHs in proteins of unknown function

on human chromosome 21 by computational approaches.

Identification of a novel putative mitogen-activated kinase cascad

Towards genome-scale structure prediction for transmembrane proteins

In this paper we briefly review some of the recent progress made by ourselves and others in developing methods for predicting the structures of transmembrane proteins from amino acid sequence. Transmembrane proteins are an important class of proteins involved in many diverse biological functions, many of which have great impact in terms of disease mechanism and drug discovery. Despite their biological importance, it has proven very difficult to solve the structures of these proteins by experimental techniques, and so there is a great deal of pressure to develop effective methods for predicting their structure. The methods we discuss range from methods for transmembrane topology prediction to new methods for low resolution folding simulations in a knowledge-based force field. This potential is designed to reproduce the properties of the lipid bilayer. Our eventual aim is to apply these methods in tandem so that useful three-dimensional models can be built for a large fraction of the transmembrane protein domains in whole proteomes

Definition of FD and PD multiple alignments: DNA-binding domains of proteins 1JHG and 1LMB from are shown

<p><b>Copyright information:</b></p><p>Taken from "Detecting DNA-binding helix–turn–helix structural motifs using sequence and structure information"</p><p>Nucleic Acids Research 2005;33(7):2129-2140.</p><p>Published online 14 Apr 2005</p><p>PMCID:PMC1079965.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p> Structures: the HTH motifs are highlighted in red. Multiple sequence alignments: all the shown alignments correspond to families Pfam seed alignments. The solid-lined boxes set the edges of multiple sequence alignments corresponding to the HTH sequences as found in the family templates 1JHG and 1LMB (red sequence)

() Jackknife results for the PD- and FD- libraries: yellow squares indicate hits detected from the PD- library, blue squares indicate hits detected from the FD- library and green squares indicate hits detected from both the libraries

<p><b>Copyright information:</b></p><p>Taken from "Detecting DNA-binding helix–turn–helix structural motifs using sequence and structure information"</p><p>Nucleic Acids Research 2005;33(7):2129-2140.</p><p>Published online 14 Apr 2005</p><p>PMCID:PMC1079965.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p> Incorrectly aligned hits are highlighted with slashes and crosses: forward slashes (/) indicate incorrectly aligned hits detected from the FD- library, backward slashes (\) indicate incorrectly aligned hits detected from the PD- library and crosses (X) indicate incorrectly aligned hits detected from both the libraries. () Jackknife results for the combination of PD- and FD- libraries and the method of 3D-templates. Green squares indicate hits detected from either the FD- library or the PD- library or both; red squares indicate hits detected from the method of 3D-templates; and brown squares indicate hits detected from all the three methods

PoreWalker: a novel tool for the identification and characterization of channels in transmembrane proteins from their three-dimensional structure

Transmembrane channel proteins play pivotal roles in maintaining the homeostasis and responsiveness of cells and the cross-membrane electrochemical gradient by mediating the transport of ions and molecules through biological membranes. Therefore, computational methods which, given a set of 3D coordinates, can automatically identify and describe channels in transmembrane proteins are key tools to provide insights into how they function