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Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Evolutionary Relationships through Genome Comparisons02:54

Evolutionary Relationships through Genome Comparisons

Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
Multi-species Conserved Sequences02:51

Multi-species Conserved Sequences

Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...

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Updated: Jun 17, 2026

DNAzyme 10-23 - Based Nanomachines for Nucleic Acid Recognition
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Finding regulatory DNA motifs using alignment-free evolutionary conservation information.

Raluca Gordân1, Leelavati Narlikar, Alexander J Hartemink

  • 1Department of Computer Science, Duke University, Box 90129, Durham, NC 27708, USA. amink@cs.duke.edu

Nucleic Acids Research
|January 6, 2010
PubMed
Summary

This study introduces a novel, alignment-free method for identifying transcription factor (TF) binding sites. The approach enhances TF binding site discovery by considering conservation irrespective of DNA sequence orientation.

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Area of Science:

  • Genomics
  • Bioinformatics
  • Computational Biology

Background:

  • Comparative genomics increasingly relies on detecting regulatory elements in intergenic sequences.
  • Current methods for transcription factor (TF) binding site discovery often use sequence alignments, which can misalign short, degenerate, or orientation-independent binding sites.

Purpose of the Study:

  • To develop a novel, alignment-free approach for TF binding site discovery using evolutionary conservation.
  • To improve the accuracy and efficiency of identifying functional DNA sites in regulatory regions.

Main Methods:

  • Developed an alignment-free method that defines conserved sites as occurring anywhere in orthologous sequences, regardless of orientation.
  • Derived informative priors over DNA sequence positions based on this relaxed definition of conservation.
  • Integrated these priors into a Gibbs sampling algorithm for motif discovery.

Main Results:

  • The novel approach demonstrated higher effectiveness on real biological data compared to alignment-dependent methods.
  • The method successfully identified transcription factor binding sites without requiring sequence alignments or phylogenetic information.

Conclusions:

  • The proposed alignment-free strategy offers a simple, fast, and more effective alternative for TF binding site discovery.
  • This method enhances the ability to detect functional regulatory elements in eukaryotic genomes.