Application of torsion angle molecular dynamics for efficient sampling of protein conformations

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.     

Retention in coupled capillary column supercritical fluid chromatography with lipids as model compounds

Summary We have investigated to which extent retention data, acquired on single capillary columns, can be used for predicting retention factors in a coupled column system. For this purpose we utilized a model mixture of 18 lipid components with widely different vapor pressures and polarities. The sample was chromatographed on two columns, SB-biphenyl-30 (70% methyl-30% biphenylpolysiloxane) and SB-cyanopropyl-50 (50% methyl-50% cyanopropylsiloxane). Experimental retention factors, acquired in coupled column systems with two columns connected in different order, were thus compared with values calculated from runs on each single column. The agreement between calculated and experimental values generally was better than 5% without any pressure drop correction.To study the possibility of predicting retention behavior in a wide pressure range from a limited number of experiments, we also investigated the relation between solute retention and mobile phase density. We found that all data could be fitted to second order equations, which gives the possibility to optimize the resolution with respect to pressure from a limited number of runs at different pressures.     

Ab initio prediction of vibrational spectra: A database approach

Efforts to develop a database of quadratic force fields for organic molecules are described. The database is based on systematic ab initio calculations, scaled to reproduce the experimentally observed frequencies. The choice of the theoretical method, the basis sets, geometries, internal coordinates and the scaling procedure are discussed. A key point in the procedure is the automatic generation of the internal valence coordinates. This is also very advantageous for geometry optimization. The database should permit the prediction of vibrational frequencies for most organic molecules to 10–20 cm⁻¹, together with semiquantitative intensities. The accuracy is sufficient to identify unknown compounds from a list of reasonable candidates.     

Raman Spectroscopic Studies of Methane Gas Hydrates

Abstract

A brief review of the Raman spectroscopic studies of methane gas hydrates is given, supported by some new measurements done in our laboratory.     

Hexagonal Si−Ge Class of Semiconducting Alloys Prepared by Using Pressure and Temperature

Multi-anvil and laser-heated diamond anvil methods have been used to subject Ge and Si mixtures to pressures and temperatures of between 12 and 17 GPa and 1500–1800 K, respectively. Synchrotron angle dispersive X-ray diffraction, precession electron diffraction and chemical analysis using electron microscopy, reveal recovery at ambient pressure of hexagonal Ge−Si solid solutions (P6₃/mmc). Taken together, the multi-anvil and diamond anvil results reveal that hexagonal solid solutions can be prepared for all Ge−Si compositions. This hexagonal class of solid solutions constitutes a significant expansion of the bulk Ge−Si solid solution family, and is of interest for optoelectronic applications.     

Stepwise Stress-Induced Transformations of Metal-Organic Polyhedral Cluster-Based Assemblies: Where Conformational and Supramolecular Features Meet

Understanding the factors governing the formation of supramolecular structures and phase transitions between various forms of molecular crystals is pivotal for developing dynamic, stimuli-responsive materials and polymorph-controlled syntheses. Here, we investigate the pressure-induced dynamic of both the intrinsic molecular structure and the supramolecular network of a predesigned polyhedral oxo-centered zinc cluster incorporating monoanionic N,N’-diphenylformamidinate and featuring N-bonded phenyl groups in close proximity to the primary coordination sphere. We demonstrate that the model oxo cluster is prone to undergoing pressure-induced conformational transformations of the secondary coordination sphere and simultaneous stepwise (initially every second polyhedral molecule undergoes the conformational transformations) and reversible transitions from an ambient phase α to high-pressure phases β and γ, as single-crystal-to-single-crystal events. The observed phase transitions illustrate the key role of an interplay between the low-energy conformation perturbations and cooperative intra- and intermolecular noncovalent interactions.     

Weak Interactions under Pressure: hp‐CuBi and Its Analogues

The metastable binary compound hp‐CuBi was obtained from the direct chemical reaction between copper and bismuth at a pressure of 5 GPa and a temperature of 720 K. The atomic arrangement comprises slabs of puckered Cu layers sandwiched between Bi planes. The QTAIM charges calculated for compounds of bismuth with transition metals reveal negligible charge transfer for hp‐CuBi. Analysis of the chemical bonding with position‐space techniques discloses multicenter interactions within the Bi‐Cu‐Bi slabs and lone‐pair interactions of the van der Waals type between these entities. hp‐CuBi exhibits metal‐type electrical conductivity with superconductivity below T_c=1.3 K.     

考虑防御系统延迟使其预测误差最大的突防弹道设计

对中段多脉冲机动突防弹道的设计问题进行了研究。采用的原理与方法有别于成熟的航天器多脉冲变轨,而是基于路径规划的思想对弹道设计问题简化。考虑敌方防御系统延迟,改进多脉冲点火模型,并基于变射面的思想对关机点参数进行了设计及优化。然后,从使敌方预测误差最大的角度提出评价函数,并利用遗传算法进行优化。最后,给出了一种同时满足导弹机动突防与打击精度要求的多脉冲弹道设计方法。从模型的可行性,方法的有效性、灵活性、迭代效率及精度等方面进行了仿真验证分析。在PC机仿真中,20 s内就设计出一条保证打击精度的中段突防弹道。结果表明,建立的模型是可行的,提出的突防弹道设计方法是快速有效的。     

Structure Prediction of Binary Pernitride MN2 Compounds (M=Ca,Sr, Ba,La, and Ti)

Metal‐pernitride compounds belong to a class of chemical systems in which both the complex ions and the non‐bonding electrons may play roles in the formation of their modified crystalline structures. To investigate this issue, the energy landscapes of pernitrides of metals with different maximum valence (M=Ca, Sr, Ba, La, and Ti) were globally explored on the ab initio level at standard and high pressures, thereby yielding possible (meta)stable modifications in these systems together with information on how the landscape changed as function of the valence of the metal cation. For all of the systems in which no compounds had been synthesized so far, we predicted the existence of kinetically stable modifications that should, in principle, be experimentally accessible. In particular, TiN₂ should crystallize in a new structure type, TiN₂‐I.     

Conference summary on the first international workshop on advanced superhard materials

Composite diamond anvils have been developed for high-pressure/high-temperature measurements of diamond anvil cells. The anvils are fabricated using single-crystal chemical vapor deposition (CVD) from previously used and/or slightly damaged anvils made of natural or synthetic diamond. These composite anvils can be fabricated to possess optical characteristics at least comparable to conventional diamond anvils, whereas the single-crystal CVD portion is more durable because of its enhanced toughness relative to natural diamond. The viability of such anvils is demonstrated in measurements on hydrogen at megabar pressures and high temperature.