title: Structure-based Markov random field model for representing evolutionary constraints on functional sites.
abstract: BACKGROUND
  Elucidating the cooperative mechanism of interconnected residues is an important component toward understanding the biological function of a protein. Coevolution analysis has been developed to model the coevolutionary information reflecting structural and functional constraints. Recently, several methods have been developed based on a probabilistic graphical model called the Markov random field (MRF), which have led to significant improvements for coevolution analysis; however, thus far, the performance of these models has mainly been assessed by focusing on the aspect of protein structure.
  
  
  RESULTS
  In this study, we built an MRF model whose graphical topology is determined by the residue proximity in the protein structure, and derived a novel positional coevolution estimate utilizing the node weight of the MRF model. This structure-based MRF method was evaluated for three data sets, each of which annotates catalytic site, allosteric site, and comprehensively determined functional site information. We demonstrate that the structure-based MRF architecture can encode the evolutionary information associated with biological function. Furthermore, we show that the node weight can more accurately represent positional coevolution information compared to the edge weight. Lastly, we demonstrate that the structure-based MRF model can be reliably built with only a few aligned sequences in linear time.
  
  
  CONCLUSIONS
  The results show that adoption of a structure-based architecture could be an acceptable approximation for coevolution modeling with efficient computation complexity.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
authors.forename: Chan-Seok
authors.initials: CS
authors.lastname: Jeong
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea. kds@kaist.ac.kr.
authors.forename: Dongsup
authors.initials: D
authors.lastname: Kim
mesh_terms: D000495:Allosteric Site / Q000235:genetics*; D005075:Biological Evolution; D019143:Evolution, Molecular; D011506:Proteins / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D011506:Proteins