title: Highly Dynamic Anion-Quadrupole Networks in Proteins.
abstract: The dynamics of anion-quadrupole (or anion-π) interactions formed between negatively charged (Asp/Glu) and aromatic (Phe) side chains are for the first time computationally characterized in RmlC (Protein Data Bank entry 1EP0 ), a homodimeric epimerase. Empirical force field-based molecular dynamics simulations predict anion-quadrupole pairs and triplets (anion-anion-π and anion-π-π) are formed by the protein during the simulated trajectory, which suggests that the anion-quadrupole interactions may provide a significant contribution to the overall stability of the protein, with an average of -1.6 kcal/mol per pair. Some anion-π interactions are predicted to form during the trajectory, extending the number of anion-quadrupole interactions beyond those predicted from crystal structure analysis. At the same time, some anion-π pairs observed in the crystal structure exhibit marginal stability. Overall, most anion-π interactions alternate between an "on" state, with significantly stabilizing energies, and an "off" state, with marginal or null stabilizing energies. The way proteins possibly compensate for transient loss of anion-quadrupole interactions is characterized in the RmlC aspartate 84-phenylalanine 112 anion-quadrupole pair observed in the crystal structure. A double-mutant cycle analysis of the thermal stability suggests a possible loss of anion-π interactions compensated by variations of hydration of the residues and formation of compensating electrostatic interactions. These results suggest that near-planar anion-quadrupole pairs can exist, sometimes transiently, which may play a role in maintaining the structural stability and function of the protein, in an otherwise very dynamic interplay of a nonbonded interaction network as well as solvent effects.
authors.affiliation: UT/ORNL Graduate School of Genome Science and Technology, University of Tennessee , F337 Walters Life Science, Knoxville, Tennessee 37996, United States.|UT/ORNL Center for Molecular Biophysics , Building 2040, Oak Ridge, Tennessee 37830, United States.
authors.forename: Karan
authors.initials: K
authors.lastname: Kapoor
authors.affiliation: Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , M407 Walters Life Sciences, Knoxville, Tennessee 37996, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duff
authors.affiliation: UT/ORNL Graduate School of Genome Science and Technology, University of Tennessee , F337 Walters Life Science, Knoxville, Tennessee 37996, United States.
authors.forename: Amit
authors.initials: A
authors.lastname: Upadhyay
authors.affiliation: Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , M407 Walters Life Sciences, Knoxville, Tennessee 37996, United States.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Bucci
authors.affiliation: Department of Animal Science, University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Arnold M
authors.initials: AM
authors.lastname: Saxton
authors.affiliation: Department of Chemistry, University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hinde
authors.affiliation: Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , M407 Walters Life Sciences, Knoxville, Tennessee 37996, United States.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Howell
authors.affiliation: Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , M407 Walters Life Sciences, Knoxville, Tennessee 37996, United States.|UT/ORNL Center for Molecular Biophysics , Building 2040, Oak Ridge, Tennessee 37830, United States.
authors.forename: Jerome
authors.initials: J
authors.lastname: Baudry
mesh_terms: D000838:Anions; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D000838:Anions; D011506:Proteins