publication . Article . 2016

Detection and sequence/structure mapping of biophysical constraints to protein variation in saturated mutational libraries and protein sequence alignments with a dedicated server

Luciano A Abriata; Christophe Bovigny; Matteo Dal Peraro;
Open Access
  • Published: 01 Jun 2016 Journal: BMC Bioinformatics, volume 17 (eissn: 1471-2105, Copyright policy)
  • Publisher: Springer Science and Business Media LLC
  • Country: Switzerland
Abstract
Background Protein variability can now be studied by measuring high-resolution tolerance-to-substitution maps and fitness landscapes in saturated mutational libraries. But these rich and expensive datasets are typically interpreted coarsely, restricting detailed analyses to positions of extremely high or low variability or dubbed important beforehand based on existing knowledge about active sites, interaction surfaces, (de)stabilizing mutations, etc. Results Our new webserver PsychoProt (freely available without registration at http://psychoprot.epfl.ch or at http://lucianoabriata.altervista.org/psychoprot/index.html) helps to detect, quantify, and sequence/stru...
Subjects
free text keywords: Biochemistry, Applied Mathematics, Molecular Biology, Structural Biology, Computer Science Applications, Sequence alignment, Protein structure, DNA microarray, Protein sequencing, Fitness landscape, Bioinformatics, Genetics, Biology, Peptide sequence, Protein design, Research Article, Deep sequencing, Next-generation sequencing, High-throughput, Protein evolution, structure-function relationships, Protein biophysics, Neutral drift
69 references, page 1 of 5

Firnberg, E, Labonte, JW, Gray, JJ, Ostermeier, M. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 2014; 31 (6): 1581-92 [OpenAIRE] [PubMed] [DOI]

Stiffler, MA, Hekstra, DR, Ranganathan, R. Evolvability as a Function of Purifying Selection in TEM-1 β-Lactamase. Cell. 2015; 160 (5): 882-92 [OpenAIRE] [PubMed] [DOI]

Jacquier, H, Birgy, A, Le Nagard, H, Mechulam, Y, Schmitt, E, Glodt, J. Capturing the mutational landscape of the beta-lactamase TEM-1. Proc Natl Acad Sci U S A. 2013; 110 (32): 13067-72 [OpenAIRE] [PubMed] [DOI]

Deng, Z, Huang, W, Bakkalbasi, E, Brown, NG, Adamski, CJ, Rice, K. Deep sequencing of systematic combinatorial libraries reveals β-lactamase sequence constraints at high resolution. J Mol Biol. 2012; 424 (3–4): 150-67 [OpenAIRE] [PubMed] [DOI]

Roscoe, BP, Thayer, KM, Zeldovich, KB, Fushman, D, Bolon, DNA. Analyses of the effects of all ubiquitin point mutants on yeast growth rate. J Mol Biol. 2013; 425 (8): 1363-77 [OpenAIRE] [PubMed] [DOI]

Podgornaia, AI, Laub, MT. Protein evolution. Pervasive degeneracy and epistasis in a protein-protein interface. Science. 2015; 347 (6222): 673-7 [OpenAIRE] [PubMed] [DOI]

7.Thyagarajan B, Bloom JD. The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin. eLife. 2014;3.

Hietpas, R, Roscoe, B, Jiang, L, Bolon, DNA. Fitness analyses of all possible point mutations for regions of genes in yeast. Nat Protoc. 2012; 7 (7): 1382-96 [OpenAIRE] [PubMed] [DOI]

Hecht, M, Bromberg, Y, Rost, B. News from the protein mutability landscape. J Mol Biol. 2013; 425 (21): 3937-48 [OpenAIRE] [PubMed] [DOI]

Olson, CA, Wu, NC, Sun, R. A comprehensive biophysical description of pairwise epistasis throughout an entire protein domain. Curr Biol CB. 2014; 24 (22): 2643-51 [OpenAIRE] [PubMed] [DOI]

Fowler, DM, Stephany, JJ, Fields, S. Measuring the activity of protein variants on a large scale using deep mutational scanning. Nat Protoc. 2014; 9 (9): 2267-84 [OpenAIRE] [PubMed] [DOI]

Araya, CL, Fowler, DM. Deep mutational scanning: assessing protein function on a massive scale. Trends Biotechnol. 2011; 29 (9): 435-42 [OpenAIRE] [PubMed] [DOI]

Fowler, DM, Fields, S. Deep mutational scanning: a new style of protein science. Nat Methods. 2014; 11 (8): 801-7 [OpenAIRE] [PubMed] [DOI]

Fowler, DM, Araya, CL, Fleishman, SJ, Kellogg, EH, Stephany, JJ, Baker, D. High-resolution mapping of protein sequence-function relationships. Nat Methods. 2010; 7 (9): 741-6 [OpenAIRE] [PubMed] [DOI]

Melnikov, A, Rogov, P, Wang, L, Gnirke, A, Mikkelsen, TS. Comprehensive mutational scanning of a kinase in vivo reveals substrate-dependent fitness landscapes. Nucleic Acids Res. 2014; 42 (14) [OpenAIRE] [PubMed] [DOI]

69 references, page 1 of 5
Abstract
Background Protein variability can now be studied by measuring high-resolution tolerance-to-substitution maps and fitness landscapes in saturated mutational libraries. But these rich and expensive datasets are typically interpreted coarsely, restricting detailed analyses to positions of extremely high or low variability or dubbed important beforehand based on existing knowledge about active sites, interaction surfaces, (de)stabilizing mutations, etc. Results Our new webserver PsychoProt (freely available without registration at http://psychoprot.epfl.ch or at http://lucianoabriata.altervista.org/psychoprot/index.html) helps to detect, quantify, and sequence/stru...
Subjects
free text keywords: Biochemistry, Applied Mathematics, Molecular Biology, Structural Biology, Computer Science Applications, Sequence alignment, Protein structure, DNA microarray, Protein sequencing, Fitness landscape, Bioinformatics, Genetics, Biology, Peptide sequence, Protein design, Research Article, Deep sequencing, Next-generation sequencing, High-throughput, Protein evolution, structure-function relationships, Protein biophysics, Neutral drift
69 references, page 1 of 5

Firnberg, E, Labonte, JW, Gray, JJ, Ostermeier, M. A comprehensive, high-resolution map of a gene’s fitness landscape. Mol Biol Evol. 2014; 31 (6): 1581-92 [OpenAIRE] [PubMed] [DOI]

Stiffler, MA, Hekstra, DR, Ranganathan, R. Evolvability as a Function of Purifying Selection in TEM-1 β-Lactamase. Cell. 2015; 160 (5): 882-92 [OpenAIRE] [PubMed] [DOI]

Jacquier, H, Birgy, A, Le Nagard, H, Mechulam, Y, Schmitt, E, Glodt, J. Capturing the mutational landscape of the beta-lactamase TEM-1. Proc Natl Acad Sci U S A. 2013; 110 (32): 13067-72 [OpenAIRE] [PubMed] [DOI]

Deng, Z, Huang, W, Bakkalbasi, E, Brown, NG, Adamski, CJ, Rice, K. Deep sequencing of systematic combinatorial libraries reveals β-lactamase sequence constraints at high resolution. J Mol Biol. 2012; 424 (3–4): 150-67 [OpenAIRE] [PubMed] [DOI]

Roscoe, BP, Thayer, KM, Zeldovich, KB, Fushman, D, Bolon, DNA. Analyses of the effects of all ubiquitin point mutants on yeast growth rate. J Mol Biol. 2013; 425 (8): 1363-77 [OpenAIRE] [PubMed] [DOI]

Podgornaia, AI, Laub, MT. Protein evolution. Pervasive degeneracy and epistasis in a protein-protein interface. Science. 2015; 347 (6222): 673-7 [OpenAIRE] [PubMed] [DOI]

7.Thyagarajan B, Bloom JD. The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin. eLife. 2014;3.

Hietpas, R, Roscoe, B, Jiang, L, Bolon, DNA. Fitness analyses of all possible point mutations for regions of genes in yeast. Nat Protoc. 2012; 7 (7): 1382-96 [OpenAIRE] [PubMed] [DOI]

Hecht, M, Bromberg, Y, Rost, B. News from the protein mutability landscape. J Mol Biol. 2013; 425 (21): 3937-48 [OpenAIRE] [PubMed] [DOI]

Olson, CA, Wu, NC, Sun, R. A comprehensive biophysical description of pairwise epistasis throughout an entire protein domain. Curr Biol CB. 2014; 24 (22): 2643-51 [OpenAIRE] [PubMed] [DOI]

Fowler, DM, Stephany, JJ, Fields, S. Measuring the activity of protein variants on a large scale using deep mutational scanning. Nat Protoc. 2014; 9 (9): 2267-84 [OpenAIRE] [PubMed] [DOI]

Araya, CL, Fowler, DM. Deep mutational scanning: assessing protein function on a massive scale. Trends Biotechnol. 2011; 29 (9): 435-42 [OpenAIRE] [PubMed] [DOI]

Fowler, DM, Fields, S. Deep mutational scanning: a new style of protein science. Nat Methods. 2014; 11 (8): 801-7 [OpenAIRE] [PubMed] [DOI]

Fowler, DM, Araya, CL, Fleishman, SJ, Kellogg, EH, Stephany, JJ, Baker, D. High-resolution mapping of protein sequence-function relationships. Nat Methods. 2010; 7 (9): 741-6 [OpenAIRE] [PubMed] [DOI]

Melnikov, A, Rogov, P, Wang, L, Gnirke, A, Mikkelsen, TS. Comprehensive mutational scanning of a kinase in vivo reveals substrate-dependent fitness landscapes. Nucleic Acids Res. 2014; 42 (14) [OpenAIRE] [PubMed] [DOI]

69 references, page 1 of 5
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