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Applications of molecular modeling to flavoproteins: Insights and challenges.

Authors
  • Sjulstok, Emil1
  • Solov'yov, Ilia A1
  • Freddolino, Peter L2
  • 1 Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark. , (Denmark)
  • 2 Department of Biological Chemistry and Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
Methods in enzymology
Publication Date
Jan 01, 2019
Volume
620
Pages
277–314
Identifiers
DOI: 10.1016/bs.mie.2019.03.014
PMID: 31072491
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The general field of molecular simulation provides a wide spectrum of methods for studying the structure and function of biomolecules. Depending on the scale and question of interest, appropriate approaches may range from ab initio quantum mechanical calculations (when detailed aspects of and changes in electronic structure must be considered) to Brownian dynamics and coarse-grained molecular dynamics (to track large scale conformational motions, diffusion, and inter-molecular interactions). The entire range of molecular simulation methods has been fruitfully applied to a range of flavoenzymes, allowing researchers to address everything from the specific intermediates involved in the photoreactions of flavin chromophore-containing light sensors, to the very long timescale motions induced by covalent modifications to bound flavin. The unique challenge posed by flavoproteins to all types of molecular simulation arises from the chemistry of the flavin isoalloxazine moiety, which presents an unusually large delocalized electron system which must be carefully treated in order to represent its contributions to the overall behavior of the system. Here we outline the particular considerations required for appropriate treatment of flavoproteins in simulations ranging from electronic structure calculations to long-timescale modeling of flavoprotein conformational transitions. © 2019 Elsevier Inc. All rights reserved.

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