Effect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations
AffiliationUniv Arizona, Dept Chem & Biochem
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationEffect of the Crystal Environment on Side-Chain Conformational Dynamics in Cyanovirin-N Investigated through Crystal and Solution Molecular Dynamics Simulations 2017, 12 (1):e0170337 PLOS ONE
Rights© 2017 Ahlstrom et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
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AbstractSide chains in protein crystal structures are essential for understanding biochemical processes such as catalysis and molecular recognition. However, crystal packing could influence side-chain conformation and dynamics, thus complicating functional interpretations of available experimental structures. Here we investigate the effect of crystal packing on side-chain conformational dynamics with crystal and solution molecular dynamics simulations using Cyanovirin-N as a model system. Side-chain ensembles for solvent-exposed residues obtained from simulation largely reflect the conformations observed in the X-ray structure. This agreement is most striking for crystal-contacting residues during crystal simulation. Given the high level of correspondence between our simulations and the X-ray data, we compare side-chain ensembles in solution and crystal simulations. We observe large decreases in conformational entropy in the crystal for several long, polar and contacting residues on the protein surface. Such cases agree well with the average loss in conformational entropy per residue upon protein folding and are accompanied by a change in side-chain conformation. This finding supports the application of surface engineering to facilitate crystallization. Our simulation-based approach demonstrated here with Cyanovirin-N establishes a framework for quantitatively comparing side-chain ensembles in solution and in the crystal across a larger set of proteins to elucidate the effect of the crystal environment on protein conformations.
NoteOpen access journal.
VersionFinal published version
SponsorsNational Institutes of Health [GM084905]; Achievement Rewards for College Scientists; Japan Society for the Promotion of Science KAKENHI [25891031, 26119006]; FOCUS Establishing Supercomputing Center of Excellence
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