Protein structure prediction from sequence variation

By Debora Marks, Thomas A. Hopf, Christopher Sander. 2012

638 citations recorded by the source corpus.

Genomic sequences contain rich evolutionary information about functional constraints on macromolecules such as proteins. This information can be efficiently mined to detect evolutionary couplings between residues in proteins and address the long-standing challenge to compute protein three-dimensional structures from amino acid sequences. Substantial progress has recently been made on this problem owing to the explosive growth in available sequences and the application of global statistical methods. In addition to three-dimensional structure, the improved understanding of covariation may help identify functional residues involved in ligand binding, protein-complex formation and conformational changes. We expect computation of covariation patterns to complement experimental structural biology in elucidating the full spectrum of protein structures, their functional interactions and evolutionary dynamics.

Subfields: Molecular Biology, Computational Biology & Bioinformatics

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Citations in the corpus

CopulaNet: Learning residue co-evolution directly from multiple sequence alignment for protein structure prediction (2020, methodology): “To extract the direct correlations, a variety of direct coupling analysis (DCA) methods have been proposed using precision matrix (the inverse of covariance matrix) or Potts model [11–15].”
Coevolutionary Landscape Inference and the Context-Dependence of Mutations in Beta-Lactamase TEM-1 (2015, methodology): “In this paper we propose a variant of DCA which assigns to each mutant sequence a statistical score, which in a next step In technical terms, a mutational landscape is given as a genotype-to-phenotype mapping.”
Robust and accurate prediction of residue–residue interactions across protein interfaces using evolutionary information (2014, background): “…model ( Thomas et al., 2008 ) to distinguish between direct and indirect couplings ( Marks et al., 2011 ; Morcos et al., 2011 ; Hopf et al., 2012 ; Nugent and Jones, 2012 ; Jones et al., 2012 ; Lapedes et al., 2012 ; Marks et al., 2012 ; Sułkowska et al., 2012 ; Kamisetty et al., 2013 ).”
Sequence co-evolution gives 3D contacts and structures of protein complexes (2014, neutral): “disentangle indirect and therefore incorrect correlations from the direct co-evolution, as has been described in work on residue–residue interactions in single proteins (Marks et al., 2012).”
Large-scale determination of previously unsolved protein structures using evolutionary information (2015, background): “…that residue–residue contacts can be accurately inferred from co-evolution patterns in sequences of related proteins ( Marks et al., 2011 ; Morcos et al., 2011 ; Hopf et al., 2012 ; Jones et al., 2012 ; Marks et al., 2012 ; Nugent and Jones, 2012 ; Sułkowska et al., 2012 ; Kamisetty et al., 2013 ).”