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Molecular dynamics analysis of CYP2D6 polymorphisms (615.4)
Author(s) -
DeWaal Parker,
Furge Laura
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.615.4
Subject(s) - molecular dynamics , docking (animal) , allele , genetics , biology , computational biology , chemistry , computational chemistry , medicine , gene , nursing
The objective of the current study was to use Molecular Dynamics (MD) computational approaches to understand how the interaction of four different CYP2D6 allelic variants with common substrates (bufuralol and N‐desmethyltamoxifen) and with an inactivator (SCH66712) compare to those of reference CYP2D6 (*1). Comparative models of each allelic variant examined (*17‐2, *17‐3, *34, *53) were constructed using AMBER force fields and the starting PDB structure 3MQ4. Analysis of RMSF revealed that allelic variants displayed areas of both greater flexibility and greater rigidity compared to *1. Greater flexibility was seen in the region of helices B’ and C and helices F and G while a region of greater rigidity was clear near helix F’/G’. Samples of final structures for each allelic variant were used for docking studies using AutoDock Vina and channel analysis using CAVER. Grant Funding Source : Supported by NIH 1R15‐GM086767‐02