DEVELOPMENT & INCORPORATION OF CARBOHYDRATE FORCE FIELDS FOR USE WITH AMBER

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 全原子琥珀力场已在别处进行了详细描述，这里只需概述对生物分子构象性质影响最大的参数。为了获得正确的动力学行为(构象和寿命)，二面体参数是价项中最重要的。在用Amber模拟低聚糖的GLYCAM参数的开发中，我们广泛地使用了量子计算来得出系数、扭转相移和平衡值的适当值。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的正确复制，而且导致生物分子与其水环境之间正确的相互作用能量。虽然部分电荷是计算静电性质的有用模型，但它们是非物理的，在它们的计算中已经采用了许多方法。在琥珀中，部分电荷是通过与量子力学静电势(ESP电荷)进行拟合来确定的。鉴于我们的GLYCAM参数化所产生的发展，要生成对多肽表现良好且与GLYCAM参数兼容的参数集，必须解决几个属性。一般来说，所有的价项将继续从量子力学计算中获得，主要在B3LYP/6-31++G**水平上进行。但有三个领域正在被重新审查，即1-4标度的使用，氧上孤子对的包含，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。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.