Efficient double hybrid density functional theory algorithms for conformational a

描述（由申请人提供）：双杂化（DH）密度泛函是用于模拟生物分子的量子力学方法中最有前途的新发展之一。DH泛函已被报道产生更准确的分子间相互作用能比前一代泛函。因此，它们即将被广泛使用。然而，除了用户不熟悉之外，仍然存在阻碍DH泛函广泛使用的实际障碍。该SBIR提案旨在通过直接解决关键的已知限制，来拥抱DH方法提供的更高准确性的机会。这些限制和我们建议的补救措施如下。(i)DH泛函的计算成本比传统的泛函更高，因为成本是分子大小的5次方，而不是3次方。我们将实施和基准一种新的三阶方法来评估DH能量没有明确的双电子积分。将根据构象相对能量评估生物药理学有用准确性的计算节省。(ii)DH泛函需要更大的原子轨道基组来产生收敛的相对能量，但是将基加倍需要16倍的计算。我们将显着改善这种缓慢的收敛，通过增加的基础，明确包括电子间坐标，通过F12技术，已被证明是成功的波函数方法。首次使用F12方法评估DH能量将进行基准测试，以评估基组大小的减少，而不会牺牲构象能量和分子间相互作用的准确性。 公共卫生相关性：以计算高效的方式实施新的DFT方法。密度泛函理论（DFT）是分子模拟的核心，广泛应用于生物学研究和药物开发中。改进后的DFT将显著提高研究人员的工作质量，扩大DFT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.