title: A practical implicit solvent potential for NMR structure calculation.
abstract: The benefits of protein structure refinement in water are well documented. However, performing structure refinement with explicit atomic representation of the solvent molecules is computationally expensive and impractical for NMR-restrained structure calculations that start from completely extended polypeptide templates. Here we describe a new implicit solvation potential, EEFx (Effective Energy Function for XPLOR-NIH), for NMR-restrained structure calculations of proteins in XPLOR-NIH. The key components of EEFx are an energy term for solvation energy that works together with other nonbonded energy functions, and a dedicated force field for conformational and nonbonded protein interaction parameters. The initial results obtained with EEFx show that significant improvements in structural quality can be obtained. EEFx is computationally efficient and can be used both to fold and refine structures. Overall, EEFx improves the quality of protein conformation and nonbonded atomic interactions. Moreover, such benefits are accompanied by enhanced structural precision and enhanced structural accuracy, reflected in improved agreement with the cross-validated dipolar coupling data. Finally, implementation of EEFx calculations is straightforward and computationally efficient. Overall, EEFx provides a useful method for the practical calculation of experimental protein structures in a physically realistic environment.
authors.affiliation: Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0307, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Division of Computational Bioscience, Building 12A, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892-5624, USA.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Schwieters
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0307, USA.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Opella
authors.affiliation: Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: fmarassi@sbmri.org.
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Marassi
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D012997:Solvents; D014867:Water / Q000737:chemistry*
chemical_list: D011506:Proteins; D012997:Solvents; D014867:Water
keywords: Calculation; EEFx; Implicit solvent; NMR; Protein structure; XPLOR-NIH
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