Temperature dependence of the dynamics and interfacial width in nanoconfined polymers via atomistic simulations.

We present a detailed computational study on the temperature effect of the dynamics and the interfacial width of unentangled cis-1,4 polybutadiene linear chains confined between strongly attractive alumina layers via long, several μs, atomistic molecular dynamics simulations for a wide range of temperatures (143-473 K). We examine the spatial gradient of the translational segmental dynamics and of an effective local glass temperature (TgL). The latter is found to be much higher than the bulk Tg for the adsorbed layer.

NMR and Docking Calculations Reveal Novel Atomistic Selectivity of a Synthetic High-Affinity Free Fatty Acid vs. Free Fatty Acids in Sudlow's Drug Binding Sites in Human Serum Albumin.

Saturation transfer difference (STD), inter-ligand NOEs (INPHARMA NMR), and docking calculations are reported for investigating specific binding sites of the high-affinity synthetic 7-nitrobenz-2-oxa-1,3-diazoyl-4-C fatty acid (NBD-C FA) with non-labeled human serum albumin (HSA) and in competition with the drugs warfarin and ibuprofen. A limited number of negative interligand NOEs between NBD-C FA and warfarin were interpreted in terms of a short-range allosteric competitive binding in the wide Sudlow's binding site II (FA7) of NBD-C FA with Ser-202, Lys-199, and Trp-214 and warfarin with Arg-218 and Arg-222. In contrast, the significant number of interligand NOEs between NBD-C FA and ibuprofen were interpreted in terms of a competitive binding mode in Sudlow's binding site I (FA3 and FA4) with Ser-342, Arg-348, Arg-485, Arg-410, and Tyr-411.

Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations-Comparison with the Liquid State.

Molecular structures, in chloroform and DMSO solution, of the free fatty acids (FFAs) caproleic acid, oleic acid, α-linolenic acid, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) are reported with the combined use of NMR and DFT calculations. Variable temperature and concentration chemical shifts of the COOH protons, transient 1D NOE experiments and DFT calculations demonstrate the major contribution of low molecular weight aggregates of dimerized fatty acids through intermolecular hydrogen bond interactions of the carboxylic groups, with parallel and antiparallel interdigitated structures even at the low concentration of 20 mM in CDCl. For the dimeric DHA, a structural model of an intermolecular hydrogen bond through carboxylic groups and an intermolecular hydrogen bond between the carboxylic group of one molecule and the ω-3 double bond of a second molecule is shown to play a role.

How to evict HP1 from H3: Using a complex salt bridge.

In an effort to unravel the unknown "binary switch" mechanisms underlying the "histone code" hypothesis of gene silencing and activation, we study the dynamics of Heterochromatin Protein 1 (HP1). We find in the literature that when HP1 is bound to tri-methylated Lysine9 (K9me3) of histone-H3 through an aromatic cage consisting of two tyrosines and one tryptophan, it is evicted upon phosphorylation of Serine10 (S10phos) during mitosis. In this work, the kick-off intermolecular interaction of the eviction process is proposed and described in detail on the basis of quantum mechanical calculations: specifically, an electrostatic interaction competes with the cation-π interaction and draws away K9me3 from the aromatic cage.

Molecular Basis for the Selectivity of DHA and EPA in Sudlow's Drug Binding Sites in Human Serum Albumin with the Combined Use of NMR and Docking Calculations.

Medium- and long-chain saturated and unsaturated free fatty acids (FFAs) are known to bind to human serum albumin (HSA), the main plasma carrier protein. Atomic-level structural data regarding the binding mode in Sudlow's sites I (FA7) and II (FA4, FA3) of the polyunsaturated ω-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), however, are largely unknown. Herein, we report the combined use of saturation transfer difference (STD) and Interligand NOEs for Pharmacophore Mapping (INPHARMA) NMR techniques and molecular docking calculations to investigate the binding mode of DHA and EPA in Sudlow's sites Ι and ΙΙ of HSA.