title: Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine.
abstract: Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine.
authors.affiliation: Department of Physics and Center for Biological Physics, Arizona State University, Tempe, AZ 85281, United States.
authors.forename: Avishek
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Physics and Center for Biological Physics, Arizona State University, Tempe, AZ 85281, United States.
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Butler
authors.affiliation: Institute for Genomics and Evolutionary Medicine, Temple University, Philadelphia, PA 19122, United States; Department of Biology, Temple University, Philadelphia, PA 19122, United States; Center for Genomic Medicine and Research, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Physics and Center for Biological Physics, Arizona State University, Tempe, AZ 85281, United States. Electronic address: Banu.Ozkan@asu.edu.
authors.forename: S Banu
authors.initials: SB
authors.lastname: Ozkan
mesh_terms: D004194:Disease / Q000235:genetics; D019143:Evolution, Molecular; D023281:Genomics / Q000379:methods*; D006801:Humans; D008511:Medicine / Q000379:methods*; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins