TY - JOUR
T1 - Integration of structural dynamics and molecular evolution via protein interaction networks
T2 - A new era in genomic medicine
AU - Kumar, Avishek
AU - Butler, Brandon M.
AU - Kumar, Sudhir
AU - Ozkan, S. Banu
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84952720717&partnerID=8YFLogxK
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U2 - 10.1016/j.sbi.2015.11.002
DO - 10.1016/j.sbi.2015.11.002
M3 - Review article
C2 - 26684487
AN - SCOPUS:84952720717
SN - 0959-440X
VL - 35
SP - 135
EP - 142
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
ER -