Efficient double hybrid density functional theory algorithms for conformational a

描述(申请人提供)：双杂化密度泛函是模拟生物分子的量子力学方法中最有前途的新发展之一。据报道，与上一代泛函相比，分子间相互作用能的计算结果要精确得多。因此，它们即将得到广泛使用。然而，除了用户缺乏熟悉度外，仍有一些实际障碍阻碍了卫生署功能的广泛使用。这项SBIR建议旨在抓住卫生署方法提供的更高准确度的机会，直接解决关键的已知限制。这些限制和我们建议的补救措施如下。(I)由于成本是分子大小的5次方，而不是分子大小的3次方，因此在计算上要比传统泛函更昂贵。我们将实现和基准一种新的三阶方法，用于计算没有显式两电子积分的氢化氢能量。对生物物理有用的准确性的计算节省将根据构象相对能量进行评估。(Ii)双氢泛函需要更大的原子轨道基组才能产生收敛的相对能量，但基数加倍需要16倍的计算。我们将显著改善这种缓慢的收敛，通过F12技术增加基明确地包括电子间坐标，这些技术已经被证明对于波函数方法是成功的。这是第一次使用F12方法来评估dH能量，将以评估在不牺牲构象能量和分子间相互作用精度的情况下可能减少的基组大小为基准。 公共卫生相关性：以计算高效的方式实施新的DFT方法。离散傅立叶变换是分子模拟的核心，在生物研究和药物开发中得到了广泛的应用。改进后的离散傅里叶变换将显著提高研究人员的工作质量，扩大离散傅里叶变换的应用范围。

DESCRIPTION (provided by applicant): Double hybrid (DH) density functionals are one of the most promising new developments in quantum mechanical methods for simulating biomolecules. DH functionals have been reported to yield much more accurate intermolecular interaction energies than previous generation functionals. They are therefore on the threshold of becoming widely used. However, there are still practical obstacles blocking widespread use of DH functionals, apart from lack of familiarity to users. This SBIR proposal aims to embrace the opportunity of greater accuracy offered by the DH approach by directly addressing the key known limitations. These limitations and our proposed remedies are as follows. (i) DH functionals are more computationally expensive to evaluate than conventional functionals because the cost scales as the 5th power, rather than the 3rd power of molecular size. We will implement and benchmark a novel 3rd order method for evaluating the DH energy without explicit two-electron integrals. The computational savings for biophysically useful accuracy will be assessed on conformational relative energies. (ii) DH functionals require larger atomic orbital basis sets to yield converged relative energies, but doubling the basis requires 16 times more computation. We will significantly ameliorate this slow convergence by augmenting the basis to explicitly include interelectronic coordinates, via F12 techniques that have proven successful for wave function methods. This first use of F12 methods to evaluate the DH energy will be benchmarked to assess the reduction in basis set size that is possible without sacrificing accuracy for conformational energies and intermolecular interactions. PUBLIC HEALTH RELEVANCE: to implement a new DFT method in a computationally efficient manner. DFT is at the core of molecular modeling and is applied widely in biological research/development and in drug discovery. The improved DFT will significantly increase researchers' quality of work and extend the application scope of DFT.