We investigate the application of torsion angle molecular dynamics (TAMD) to augment conformational sampling of peptides and proteins. Interesting conformational changes in proteins mainly involve torsional degrees of freedom. Carrying out molecular dynamics in torsion space does not only explicitly sample the most relevant degrees of freedom, but also allows larger integration time steps with elimination of the bond and angle degrees of freedom. However, the covalent geometry needs to be fixed during internal coordinate dynamics, which can introduce severe distortions to the underlying potential surface in the extensively parameterized modern Cartesian-based protein force fields. A "projection" approach (Katritch et al. J Comput Chem 2003, 24, 254-265) is extended to construct an accurate internal coordinate force field (ICFF) from a source Cartesian force field. Torsion crossterm corrections constructed from local molecular fragments, together with softened van der Waals and electrostatic interactions, are used to recover the potential surface and incorporate implicit bond and angle flexibility. MD simulations of dipeptide models demonstrate that full flexibility in both the backbone phi/psi and side chain chi1 angles are virtually restored. The efficacy of TAMD in enhancing conformational sampling is then further examined by folding simulations of small peptides and refinement experiments of protein NMR structures. The results show that an increase of several fold in conformational sampling efficiency can be reliably achieved. The current study also reveals some complicated intrinsic properties of internal coordinate dynamics, beyond energy conservation, that can limit the maximum size of the integration time step and thus the achievable gain in sampling efficiency. 相似文献
The use of oil-soluble radical generators for emulsion polymerization is considered. When radicals are formed in pairs within particles of a seed latex, the occurrence of radical desorption leads to complex kinetics. Use of radical balances and realistic simplifications produce a method for a relatively simple calculation of radical populations in the particles. Examples are restricted, for illustration purposes, to cases where the average number of radicals per particle, n , is less than one. Very low rates of radical desorption cause a substantial increase in n . As the desorption rate increases, the value of n decreases. n increases slowly with radical generation rate. Large decreases in the chain termination rate coefficient (which may accompany a gel effect) can have a negligible effect on the value of n . Radical distributions obtained from oil-soluble initiators can be slightly broader than those expected from the use of water-soluble initiators. The kinetics of emulsion polymerization will be similar for the two types of radical generator when radicals from oil-soluble generators can desorb from the polymer particles. 相似文献
This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6HnF5?nSO2NH2) with bovine carbonic anhydrase II (BCA). Quantitative structure–activity relationships between the free energy, enthalpy, and entropy of binding and pKa and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two independent effects of fluorination on the ligand: its electrostatic potential and its hydrophobicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the ZnII cofactor–sulfonamide bond (≈65 % of the free energy of binding), the hydrogen bonds between the ligand and BCA (≈10 %), and the contacts between the phenyl ring of the ligand and BCA (≈25 %). Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by 19F NMR spectroscopy and X‐ray crystallography (for complexes with human carbonic anhydrase II). 相似文献
The microwave spectrum of gaseous bromomethyl cyclopropane is reported in the range 12 to 36 GHz. Lines of the 79Br and 81Br species of cis and gauche forms are assigned and partial r0-structures derived. The rotational constants in MHz are: gauche C3H5CH279Br, A = 11 469.285, B = 1 374.777, C = 1 295.394; gauche C3H5CH281Br, A = 11 400.100, B = 1 364.088, C = 1 283.952; cis C3H5CH279Br, A = 8 759.918, B = 1 597.413, C = 1 522.141; cis C3H5CH281Br, A = 8 716.552, B = 1 583.761, C = 1 509.017. 相似文献