Yilmazer Nusret Duygu, Korth Martin
Institute for Theoretical Chemistry, Ulm University, Albert-Einstein-Allee 11, 89069 Ulm, Germany.
Int J Mol Sci. 2016 May 16;17(5):742. doi: 10.3390/ijms17050742.
We review the first successes and failures of a "new wave" of quantum chemistry-based approaches to the treatment of protein/ligand interactions. These approaches share the use of "enhanced", dispersion (D), and/or hydrogen-bond (H) corrected density functional theory (DFT) or semi-empirical quantum mechanical (SQM) methods, in combination with ensemble weighting techniques of some form to capture entropic effects. Benchmark and model system calculations in comparison to high-level theoretical as well as experimental references have shown that both DFT-D (dispersion-corrected density functional theory) and SQM-DH (dispersion and hydrogen bond-corrected semi-empirical quantum mechanical) perform much more accurately than older DFT and SQM approaches and also standard docking methods. In addition, DFT-D might soon become and SQM-DH already is fast enough to compute a large number of binding modes of comparably large protein/ligand complexes, thus allowing for a more accurate assessment of entropic effects.
我们回顾了基于量子化学的“新一波”方法在处理蛋白质/配体相互作用方面的首次成功与失败。这些方法共同使用了“增强型”、色散（D）和/或氢键（H）校正的密度泛函理论（DFT）或半经验量子力学（SQM）方法，并结合某种形式的系综加权技术来捕捉熵效应。与高级理论以及实验参考相比的基准和模型系统计算表明，DFT-D（色散校正密度泛函理论）和SQM-DH（色散和氢键校正半经验量子力学）的表现比旧的DFT和SQM方法以及标准对接方法准确得多。此外，DFT-D可能很快就能，而SQM-DH已经能够足够快速地计算相当大的蛋白质/配体复合物的大量结合模式，从而更准确地评估熵效应。
