title: Urea-Aromatic Stacking and Concerted Urea Transport: Conserved Mechanisms in Urea Transporters Revealed by Molecular Dynamics.
abstract: Urea transporters are membrane proteins that selectively allow urea molecules to pass through. It is not clear how these transporters allow rapid conduction of urea, a polar molecule, in spite of the presence of a hydrophobic constriction lined by aromatic rings. The current study elucidates the mechanism that is responsible for this rapid conduction by performing free energy calculations on the transporter dvUT with a cumulative sampling time of about 1.3 μs. A parallel arrangement of aromatic rings in the pore enables stacking of urea with these rings, which, in turn, lowers the energy barrier for urea transport. Such interaction of the rings with urea is proposed to be a conserved mechanism across all urea-conducting proteins. The free energy landscape for the permeation of multiple urea molecules reveals an interplay between interurea interaction and the solvation state of the urea molecules. This is for the first time that multiple molecule permeation through any small molecule transporter has been modeled.
authors: Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology , Hyderabad 500032, India.
authors: Siladitya
authors: S
authors: Padhi
authors: Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology , Hyderabad 500032, India.
authors: U Deva
authors: UD
authors: Priyakumar
mesh_terms: D001665:Binding Sites; D001692:Biological Transport; D006860:Hydrogen Bonding; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D017434:Protein Structure, Tertiary; D013816:Thermodynamics; D014508:Urea / Q000737:chemistry / Q000378:metabolism*; D000096982:Urea Transporters
chemical_list: D026901:Membrane Transport Proteins; D010649:Phenylalanine; D010713:Phosphatidylcholines; D014508:Urea; D000096982:Urea Transporters; C028694:1-palmitoyl-2-oleoylphosphatidylcholine