title: HIV-1 Capsid Function Is Regulated by Dynamics: Quantitative Atomic-Resolution Insights by Integrating Magic-Angle-Spinning NMR, QM/MM, and MD.
abstract: HIV-1 CA capsid protein possesses intrinsic conformational flexibility, which is essential for its assembly into conical capsids and interactions with host factors. CA is dynamic in the assembled capsid, and residues in functionally important regions of the protein undergo motions spanning many decades of time scales. Chemical shift anisotropy (CSA) tensors, recorded in magic-angle-spinning NMR experiments, provide direct residue-specific probes of motions on nano- to microsecond time scales. We combined NMR, MD, and density-functional-theory calculations, to gain quantitative understanding of internal backbone dynamics in CA assemblies, and we found that the dynamically averaged15N CSA tensors calculated by this joined protocol are in remarkable agreement with experiment. Thus, quantitative atomic-level understanding of the relationships between CSA tensors, local backbone structure, and motions in CA assemblies is achieved, demonstrating the power of integrating NMR experimental data and theory for characterizing atomic-resolution dynamics in biological systems.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.|Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine , 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.
authors.forename: Huilan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.|Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine , 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.
authors.forename: Guangjin
authors.initials: G
authors.lastname: Hou
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.|Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine , 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.
authors.forename: Manman
authors.initials: M
authors.lastname: Lu
authors.affiliation: Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine , 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.|Department of Structural Biology, University of Pittsburgh School of Medicine , 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine , 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.|Department of Structural Biology, University of Pittsburgh School of Medicine , 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.
authors.forename: In-Ja L
authors.initials: IL
authors.lastname: Byeon
authors.affiliation: Computer Science Department, Carnegie Mellon University , Gates Hillman Center, 5000 Forbes Avenue, Pittsburgh, Pennsylvania 15213, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Langmead
authors.affiliation: Department of Physics and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Perilla
authors.affiliation: National High Magnetic Field Laboratory, Florida State University , Tallahassee, Florida 32310, United States.
authors.forename: Ivan
authors.initials: I
authors.lastname: Hung
authors.affiliation: National High Magnetic Field Laboratory, Florida State University , Tallahassee, Florida 32310, United States.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Gor'kov
authors.affiliation: National High Magnetic Field Laboratory, Florida State University , Tallahassee, Florida 32310, United States.
authors.forename: Zhehong
authors.initials: Z
authors.lastname: Gan
authors.affiliation: National High Magnetic Field Laboratory, Florida State University , Tallahassee, Florida 32310, United States.
authors.forename: William W
authors.initials: WW
authors.lastname: Brey
authors.affiliation: Department of Chemistry and Chemical Biology, Rutgers University , 174 Frelinghuysen Road, Piscataway, New Jersey 08854-8087, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Case
authors.affiliation: Department of Physics and Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
authors.affiliation: Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine , 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.|Department of Structural Biology, University of Pittsburgh School of Medicine , 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gronenborn
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware , Newark, Delaware 19716, United States.|Pittsburgh Center for HIV Protein Interactions, University of Pittsburgh School of Medicine , 1051 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15261, United States.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Polenova