Using First Passage Statistics to Extract Environmentally Dependent Amino Acid Correlations

In this work, we study the first passage statistics of amino acid primary sequences, that is the probability of observing an amino acid for the first time at a certain number of residues away from a fixed amino acid. By using this rich mathematical framework, we are able to capture the background di...

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Bibliographic Details
Published in:PloS one Vol. 9; no. 7; p. e101665
Main Authors: Greenbaum, Benjamin D., Kumar, Pradeep, Libchaber, Albert
Format: Journal Article
Language:English
Published: United States Public Library of Science 07.07.2014
Public Library of Science (PLoS)
Subjects:
Amino Acids
Arginine
Biology
Biology and Life Sciences
Chemical bonds
Computational Biology - methods
Correlation
Correlation analysis
Cysteine
Ecosystem
Environment
Environmental statistics
Genomes
Genomics
Glutamic acid
High temperature
High temperature environments
Markov analysis
Natural selection
Organisms
Phylogeny
Physical Sciences
Physics
Physiochemistry
Probability
Proteins
Residues
Sequences
Statistics
Studies
Temperature
Temperature dependence
Thermal stability
New York
United States > US
New Jersey
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:In this work, we study the first passage statistics of amino acid primary sequences, that is the probability of observing an amino acid for the first time at a certain number of residues away from a fixed amino acid. By using this rich mathematical framework, we are able to capture the background distribution for an organism, and infer lengths at which the first passage has a probability that differs from what is expected. While many features of an organism's genome are due to natural selection, others are related to amino acid chemistry and the environment in which an organism lives, constraining the randomness of genomes upon which selection can further act. We therefore use this approach to infer amino acid correlations, and then study how these correlations vary across a wide range of organisms under a wide range of optimal growth temperatures. We find a nearly universal exponential background distribution, consistent with the idea that most amino acids are globally uncorrelated from other amino acids in genomes. When we are able to extract significant correlations, these correlations are reliably dependent on optimal growth temperature, across phylogenetic boundaries. Some of the correlations we extract, such as the enhanced probability of finding, for the first time, a cysteine three residues away from a cysteine or glutamic acid two residues away from an arginine, likely relate to thermal stability. However, other correlations, likely appearing on alpha helical surfaces, have a less clear physiochemical interpretation and may relate to thermal stability or unusual metabolic properties of organisms that live in a high temperature environment.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: BG AL. Performed the experiments: BG. Analyzed the data: BG AL PK. Wrote the paper: BG PK AL.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0101665