title: Interplay of Electrostatics and Hydrophobic Effects in the Metamorphic Protein Human Lymphotactin.
abstract: The human lymphotactin (hLtn) is a protein that features two native states both of which are physiologically relevant: it is a monomer (hLtn10) at 10 °C with 200 mM salt and a dimer (hLtn40) at 40 °C and without salt. Here we focus on the networks of electrostatic and hydrophobic interactions that display substantial changes upon the conversion from hLtn10 to hLtn40 since they are expected to modulate the relative stability of the two folds. In addition to the Arg 23-Arg 43 interaction discussed in previous work, we find several other like-charge pairs that are likely important to the stability of hLtn10. Free energy perturbation calculations are carried out to explicitly evaluate the contribution of the Arg 23-Arg 43 interaction to the hLtn10 stability. hLtn40 features a larger number of salt bridges, and a set of hydrophobic residues undergo major changes in the solvent accessible surface area between hLtn10 and hLtn40, pointing to their importance to the relative stability of the two folds. We also discuss the use of explicit and implicit solvent simulations for characterizing the conformational ensembles under different solution conditions.
authors.affiliation: †Graduate Program in Biophysics, University of Wisconsin-Madison, 1525 Linden Drive, Madison, Wisconsin 53706, United States.
authors.forename: Elif Nihal
authors.initials: EN
authors.lastname: Korkmaz
authors.affiliation: ‡Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, Wisconsin 53226, United States.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Volkman
authors.affiliation: †Graduate Program in Biophysics, University of Wisconsin-Madison, 1525 Linden Drive, Madison, Wisconsin 53706, United States.|§Department of Chemistry and Theoretical Chemistry Institute, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cui
mesh_terms: D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008222:Lymphokines / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D055550:Protein Stability; D017433:Protein Structure, Secondary; D012795:Sialoglycoproteins / Q000737:chemistry*; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D008222:Lymphokines; D012795:Sialoglycoproteins; C018997:lymphotactin