Effect of DMSO on Water Molecules Near Phospholipid Bilayer Surfaces

Wednesday, March 2, 2016 kinetic rather than thermodynamic control. We have also used the new protocol to simulate disulfide bonding in the terminal guanylin segment within the 94amino-acid prohormone proguanylin. It is envisaged that in future an efficient reactive force field can be constructed along these lines to model protein oxidative folding. 3182-Pos Board B559 Sequence-Specific Binding and Diffusion of TRF1 on Telomeric DNA Studied by Molecular Dynamics Milosz Wieczor, Jacek Czub. Gdansk University of Technology, Gdansk, Poland. Telomeres are nucleoprotein complexes that cap the ends of linear chromosomes. Their protective and structural function depends on several protein factors that form the so-called shelterin complex, anchored to telomeric DNA via three different proteins: double-strand binding TRF1 and TRF2, and singlestrand binding POT1. Homologous DNA-binding domains of TRF1 and TRF2 share the homeodomain fold commonly found among DNA-interacting factors, and both recognize the repeating telomeric motif (5’-TTAGGG-3’) in a structurally similar fashion. Therefore, while both domains exhibit a high degree of similarity to other DNA-binding folds, they differ from them in the availability of target binding sites, which in the case of telomerebinding proteins are arranged in long (several kbp) tandem arrays. In such a system, diffusion between neighboring binding sites becomes a relevant aspect of protein dynamics at telomeres, facilitating e.g. the assembly of shelterin units on telomeric DNA. In this work, we present a comprehensive study of the sequence specific binding of TRF1 to telomeric DNA and the diffusion of TRF1 along the telomeric sequence. We try to identify the factors that facilitate the formation of sequence-specific protein-DNA complex, and explore the free energy landscape of TRF1 on telomeric DNA using both simulations of spontaneous complex formation and umbrella sampling along a helical path on DNA. The obtained results agree well with experimental data on the kinetics of diffusion on telomeric DNA, allowing us to extract the large-scale coarse grained picture of protein-DNA interaction in the telomeric region. 3183-Pos Board B560 Simulation Studies of Twist-Stretch Coupling in Nucleic Acids Anupam Chatterjee. Chemistry, UC Irvine, Irvine, CA, USA. The helical structures of DNA and double stranded RNA and their chiral nature lead to very specific and interesting mechanical properties. One such property is the twist-stretch coupling which, in case of DNA, has been found to be important in biological processes like DNA-protein binding and DNA packaging in viruses. Naively, as suggested by a simple picture of wringing out a cloth, both DNA and RNA should be expected to lengthen when unwound. Recent experiments on single DNA molecules has shown, however, that BDNA in fact counter-intuitively shortens when twisted over a range around its native structure. This negative twist-stretch coupling of DNA has also been observed in some single molecule DNA simulation studies. A recent experiment on double stranded RNA has revealed that unlike DNA, RNA shortens when unwound, revealing a surprising difference between otherwise chemically similar molecules. In our study, we plan to probe the twist-stretch coupling of both DNA and dsRNA using atomistic MD simulations. We will use harmonic twist constraints on individual molecules of double stranded B-DNA, A-RNA as well as the lefthanded double helix Z-DNA of various nucleotide sequences, and then plot applied twist v/s stretch to get the values of twist-stretch coupling. This combined with a detailed analysis of the resultant atomistic structures will enable us to shed further light into the molecular details of this surprising effect. 3184-Pos Board B561 Solvation Structure and Quasidynamics of Biomolecules Steered with Effective Solvation Forces Obtained From Molecular Theory of Solvation Andriy Kovalenko1,2. 1 National Institute for Nanotechnology, Edmonton, AB, Canada, 2 Mechanical Engineering, University of Alberta, Edmonton, AB, Canada. Three-dimensional reference interaction site model with Kovalenko-Hirata closure (3D-RISM-KH molecular theory of solvation) is Ornstein-Zernike type integral equation theory of liquids. Based on first principles of statistical mechanics, 3D-RISM-KH consistently accounts for effect of chemical specificities of solvent, co-solvent, ions, and ligands on biomolecules solvation structure and thermodynamics, including steric forces, hydrophobicity, hydrogen bonding, and other effective interactions. 3D-RISM-KH supplemented with the partial molar volume correction, a.k.a. ‘‘Universal Correction’’ (UC), provides an excellent agreement with experimental data on a large set of small compounds for solvation free energies in octanol and water, and octanol-

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water partition coefficients. 3D-RISM-KH structural water detection and placement are implemented in Amber Tools and Molecular Operating Environment (MOE) packages. Structural water plays critical role in protein interactions and functions; case studies include HET-s prion, Ab oligomer and fibril formation, folding promotion in GroEL chaperonin, and ligand binding to maltose-binding protein. Multi-time-step MD of biomolecules steered with mean solvation forces obtained from 3D-RISM-KH at outer steps and treated with generalized solvation force extrapolation (GSFE) at inner steps is efficiently stabilized with the optimized isokinetic Nose´-Hoover chain (OIN) thermostat. The accuracy of GSFE and efficiency of OIN allow picoseconds outer steps while accurately reproducing conformational properties, as validated on hydrated alanine dipeptide, miniprotein 1L2Y, and protein G. Due to 3D-RISM-KH statistical averaging over rare events of solvent exchange and localization in biomolecular spaces, this quasidynamics results in time scale compression of protein conformational changes coupled with solvent and so in huge acceleration of conformational sampling. This provides up to 1000-fold effective speedup of sampling, compared to conventional MD with explicit solvent, and enables to fold the miniprotein from a fully denatured state in 60ns quasidynamics, cf. 4-9ms folding time in experiment. 3185-Pos Board B562 Effect of DMSO on Water Molecules Near Phospholipid Bilayer Surfaces Yuno Lee, Changbong Hyeon. KIAS, Seoul, Korea, Republic of. Using all atom molecular dynamics simulations at various DMSO concentrations, we study the structural and dynamical properties of water and DMSO in the vicinity of phospholipid bilayers. In accord with the recent experimental studies, we confirmed the DMSO-induced dehydration and the enhancement of water diffusivity unique to lipid-DMSO-H2O system, and further revealed the microscopic origin of these observations. At higher DMSO concentrations the extent of DMSO depletion from the phospholipid bilayer surface further increases, resulting in a development of the hydration layer in which the composition of water is greater than in the bulk. Modeling TEMPO-PC explicitly in the simulations, our study also reveals that due to the hydrophobic moiety, ˚ interior from the head groups. the spin label tends to be buried ~ 7 A 3186-Pos Board B563 Proteins Near Solid Surfaces and at Air-Water Interfaces Marek Cieplak1, Grzegorz Nawrocki2. 1 Institute of Physics, PAS, Warsaw, Poland, 2Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA. A systematic comparison of the adsorptive properties of various surfaces can be accomplished by considering a set of reference biomolecules. We have initiated such a program by selecting the twenty natural amino acids, some dipeptides, and a small protein - tryptophan cage as the reference systems for all-atom simulational studies. The surfaces compared are: ZnS, gold, cellulose Ib, mica, and four faces of ZnO. The specificities, as determined through the potential of the mean force for the amino acids, are found to depend on the solid, its face and, for gold, on the choice of the force field (hydrophobic, hydrophilic, or incorporating the polarizability of the metal). We demonstrate that binding energies of dipeptides and tripeptides are smaller than the combined binding energies of their amino acidic components. The water density and polarization profiles are also surface-specific. The first water layer that forms near the strongly hydrophilic ZnO corresponds to packing at such a density that even single residues cannot reach the solid. ZnS is more hydrophobic and yields only minor articulation of water into layers. For the hydrophobic Au, adsorption events of tryptophan cage are driven by attraction to the strongest binding amino acids. This is not so for ZnO, ZnS and for the hydrophilic models of gold. Studies of several proteins near mica, with a net charge on its surface, indicate existence of two types of states: deformed and unfolded. Using a coarse-grained model, we also study the glassy behavior of protein layers at air-water interfaces. 3187-Pos Board B564 Vibrations of Water Molecules in Monosaccharide Hydration Shell by DFT-MD Studies Katsufumi Tomobe1, Takashi Iijima2, Eiji Yamamoto1, Masato Yasui2, Kenji Yasuoka1. 1 Mechanical Engineering, Keio University, Tokyo, Japan, 2School of Medicine, Keio University, Tokyo, Japan. Carbohydrates are one of the richest biological materials. Hexoses (glucose, mannose, galactose) are the richest monosaccharide in our body. Because they play an important roll for our energy cycle with water molecules, influence of hydration becomes key for carbohydrate mechanism. Due to the development of near infrared spectroscopy, the difference of hydration between monosaccharide can be observed, but a molecular mechanism of hydration change is unclear. Here we performed ab initio molecular dynamics simulations of