The tangled bank of amino acids

Protein Science : a Publication of the Protein Society
Richard A Goldstein, David D Pollock


The use of amino acid substitution matrices to model protein evolution has yielded important insights into both the evolutionary process and the properties of specific protein families. In order to make these models tractable, standard substitution matrices represent the average results of the evolutionary process rather than the underlying molecular biophysics and population genetics, treating proteins as a set of independently evolving sites rather than as an integrated biomolecular entity. With advances in computing and the increasing availability of sequence data, we now have an opportunity to move beyond current substitution matrices to more interpretable mechanistic models with greater fidelity to the evolutionary process of mutation and selection and the holistic nature of the selective constraints. As part of this endeavour, we consider how epistatic interactions induce spatial and temporal rate heterogeneity, and demonstrate how these generally ignored factors can reconcile standard substitution rate matrices and the underlying biology, allowing us to better understand the meaning of these substitution rates. Using computational simulations of protein evolution, we can demonstrate the importance of both spatial and tem...Continue Reading


Mar 17, 2017·Annual Review of Biophysics·Julian Echave, Claus O Wilke
Jun 21, 2018·Molecular Biology and Evolution·Stephanie J Spielman, Sergei L Kosakovsky Pond
Nov 24, 2017·F1000Research·Dariya K SydykovaClaus O Wilke
Feb 10, 2018·BMC Evolutionary Biology·Alexander PlattDavid A Liberles
Mar 12, 2020·Journal of Molecular Evolution·Ľubomír Tomáška, Jozef Nosek
Aug 24, 2018·Genes·Anna PosfaiDavid M McCandlish
Feb 24, 2017·Journal of the Royal Society, Interface·Ashley I Teufel, Claus O Wilke
Oct 25, 2017·Nature Ecology & Evolution·Richard A Goldstein, David D Pollock
Sep 9, 2020·Molecular Biology and Evolution·Peter B ChiDavid A Liberles
Sep 9, 2020·Molecular Biology and Evolution·Noor YoussefJoseph P Bielawski
Nov 25, 2020·Journal of Molecular Evolution·Mackenzie M Johnson, Claus O Wilke


Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S Henikoff, J G Henikoff
Jun 1, 1992·Computer Applications in the Biosciences : CABIOS·D T JonesJ M Thornton
Jan 1, 1981·Journal of Molecular Evolution·J Felsenstein
Jan 1, 1995·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Sean R EddyR Durbin
Nov 4, 1994·Journal of Molecular Biology·S Henikoff, J G Henikoff
Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·P BaldiM A McClure
Jul 1, 1996·Biophysical Journal·B J Strait, T G Dewey
Dec 24, 1997·Mathematical Biosciences·C Tuffley, M Steel
Jul 10, 1998·Molecular Biology and Evolution·A L Halpern, W J Bruno
Mar 13, 1999·Journal of Molecular Biology·David D PollockNick Goldman
May 15, 2003·Systematic Biology·John P HuelsenbeckJonathan P Bollback
Jun 23, 2006·PLoS Computational Biology·Paul D WilliamsRichard A Goldstein
Jan 8, 2008·Molecular Biology and Evolution·Ziheng Yang, Rasmus Nielsen
Mar 28, 2008·Molecular Biology and Evolution·Si Quang Le, Olivier Gascuel
May 27, 2008·Molecular Biology and Evolution·Simon Whelan
Aug 23, 2008·Bioinformatics·Le Si QuangNicolas Lartillot
Sep 29, 2009·Molecular Biology and Evolution·A P Jason de KoningDavid D Pollock
Nov 17, 2009·PLoS Computational Biology·Asif U TamuriRichard A Goldstein
Feb 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Nicolas RodrigueNicolas Lartillot
Nov 27, 2010·Molecular Biology and Evolution·Mario dos ReisRichard A Goldstein
Nov 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Faruck MorcosMartin Weigt
May 2, 2012·Proceedings of the National Academy of Sciences of the United States of America·David D PollockRichard A Goldstein
Sep 15, 2012·Bioinformatics·A P Jason de KoningDavid D Pollock
Oct 16, 2012·Nature·Michael S BreenFyodor A Kondrashov
May 18, 2013·Current Opinion in Structural Biology·William R TaylorMichael I Sadowski
May 31, 2013·Nature·David M McCandlishJoshua B Plotkin
Nov 22, 2013·Statistical Applications in Genetics and Molecular Biology·Nengjun YiHimel Mallick
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Dec 11, 2013·Proceedings of the National Academy of Sciences of the United States of America·Orr AshenbergJesse D Bloom
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·David D Pollock, Richard A Goldstein
Dec 3, 2014·Trends in Genetics : TIG·Dmitry A Kondrashov, Fyodor A Kondrashov
Mar 5, 2015·Molecular Biology and Evolution·Richard A GoldsteinDavid D Pollock
Jun 10, 2015·Proceedings of the National Academy of Sciences of the United States of America·Premal ShahJoshua B Plotkin

Related Concepts

In Silico
Amino Acids, I.V. solution additive
Spatial Distribution
Gene Products, Protein
Protein Structure Databases
Pilomatrix Carcinoma of Skin

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Related Papers

Protein Science : a Publication of the Protein Society
David A LiberlesSimon Whelan
Protein Science : a Publication of the Protein Society
Tyler N Starr, Joseph W Thornton
Evolution; International Journal of Organic Evolution
Alex Wong, Kimberley Seguin
© 2020 Meta ULC. All rights reserved