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Related Concept Videos

Signal Sequences and Sorting Receptors01:41

Signal Sequences and Sorting Receptors

Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
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Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
Comparing Copy Number Variations and SNPs02:26

Comparing Copy Number Variations and SNPs

Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
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.
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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.

Prateek Kumar1, Steven Henikoff, Pauline C Ng

  • 1Department of Genomic Medicine, J. Craig Venter Institute, San Diego, California, USA.

Nature Protocols
|June 30, 2009
PubMed
Summary
This summary is machine-generated.

Non-synonymous single nucleotide polymorphisms (nsSNPs) can alter protein function and an organism's phenotype. The Sorting Tolerant From Intolerant (SIFT) algorithm predicts the functional impact of amino acid substitutions caused by nsSNPs.

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Area of Science:

  • Genetics
  • Bioinformatics
  • Molecular Biology

Background:

  • Genetic mutations, specifically non-synonymous single nucleotide polymorphisms (nsSNPs), can lead to amino acid substitutions (AAS) in proteins.
  • These AAS have the potential to alter protein function and consequently affect an organism's observable traits (phenotype).

Purpose of the Study:

  • To describe a protocol for utilizing the Sorting Tolerant From Intolerant (SIFT) algorithm.
  • To predict the functional impact of amino acid substitutions resulting from nsSNPs.

Main Methods:

  • The SIFT algorithm leverages sequence homology to identify conserved positions within protein sequences.
  • It predicts the effect of all possible substitutions at each position, assuming conserved sites are crucial for protein function.

Main Results:

  • SIFT provides predictions on whether an amino acid substitution is likely to affect protein function.
  • The protocol is efficient, typically taking 5-20 minutes for completion.

Conclusions:

  • The SIFT algorithm is a valuable tool for predicting the functional consequences of nsSNPs.
  • This prediction method aids in understanding the relationship between genetic variation and phenotypic outcomes.