DEVELOPMENT & INCORPORATION OF CARBOHYDRATE FORCE FIELDS FOR USE WITH AMBER

发展

• 批准号: 8168844
• 负责人: ROBERT J WOODS
• 金额: $ 6.74万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-10 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168844
• 关键词: Address; Amber; Area; Behavior; Carbohydrates; Charge; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Electrostatics; Environment; Equilibrium; Funding; Grant; Institution; Light; Mechanics; Methods; Modeling; Molecular Conformation; Nature; Oligosaccharides; Oxygen; Peptides; Phase; Property; Proteins; Relative (related person); Reproduction; Research; Research Personnel; Resources; Source; Torsion; United States National Institutes of Health; aqueous; quantum; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The all atom AMBER force field has been described in detail elsewhere, and it is only necessary here to outline the parameters that most strongly influence the conformational properties of biomolecules. To achieve correct dynamic behavior (conformations and lifetimes), the dihedral parameters are the most important of the valence terms. In the development of the GLYCAM parameters for oligosaccharide simulations with AMBER, we made extensive use of quantum calculations to derive appropriate values for the coefficients, torsional phase shifts, and equilibrium values. Due to the polar nature of oligosaccharides and proteins, electrostatic interactions, determined by partial atomic charges, are as important as the torsion terms. It is essential that these charges result not only in a correct reproduction of relative conformational energies, but also in the correct interaction energies between the biomolecule and its aqueous environment. Although partial charges are a useful model for computing electrostatic properties, they are non-physical and there have been numerous methods employed in their calculation. Within AMBER the partial charges are determined by fitting to quantum mechanical electrostatic potentials (ESP-charges). In light of the developments arising from our parameterization of GLYCAM, to generate a parameter set that performs well on peptides, and that is compatible with the GLYCAM parameters, several properties will have to be addressed. In general, all of the valence terms will continue to be derived from quantum mechanical calculations, mostly performed at the B3LYP/6-31++G** level. But three areas in particular are being reexamined, namely, the use of 1-4 scaling, the inclusion of lone pairs on oxygen, and the complex relationship between 1-4 scaling, torsion terms, electrostatic interactions and charge polarization.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 全原子琥珀力场已在别处详细描述，这里只需概述对生物分子构象特性影响最大的参数。 为了实现正确的动态行为（构象和寿命），二面角参数是最重要的价项。 在开发用于 AMBER 寡糖模拟的 GLYCAM 参数时，我们广泛使用量子计算来导出适当的系数值、扭转相移和平衡值。 由于寡糖和蛋白质的极性性质，由部分原子电荷决定的静电相互作用与扭转项一样重要。 至关重要的是，这些电荷不仅导致相对构象能量的正确再现，而且导致生物分子与其水环境之间的正确相互作用能量。 尽管部分电荷是计算静电特性的有用模型，但它们是非物理的，并且在其计算中采用了多种方法。在 AMBER 中，部分电荷是通过拟合量子力学静电势（ESP 电荷）来确定的。 鉴于我们的 GLYCAM 参数化所取得的进展，为了生成在肽上表现良好且与 GLYCAM 参数兼容的参数集，必须解决几个属性。一般来说，所有价项将继续源自量子力学计算，主要在 B3LYP/6-31++G** 级别进行。但正在重新审视三个领域，即 1-4 标度的使用、氧上孤对电子的包含，以及 1-4 标度、扭转项、静电相互作用和电荷极化之间的复杂关系。