Rapid and accurate assessment of GPCR-ligand interactions Using the fragment molecular orbital-based density-functional tight-binding method.
Rapid and accurate assessment of GPCR-ligand interactions Using the fragment molecular orbital-based density-functional tight-binding method.
复制标题
DOI：
10.1002/jcc.24850
复制
发表时间：
2017-09-05
影响因子：
3
通讯作者：
Heifetz A
中科院分区：
文献类型：
--
作者：
Morao I;Fedorov DG;Robinson R;Southey M;Townsend-Nicholson A;Bodkin MJ;Heifetz A
可靠和准确地评估受体-配体相互作用和配对相互作用能是合理药物设计的基本要素。虽然量子力学(QM)方法是实现这一目标的一种很有前途的方法，但传统的QM方法由于其高昂的计算成本而不适用于大型生物系统。在这里，片断分子轨道(FMO)方法被用来加速QM计算，通过将FMO与密度泛函紧束缚(DFTB)方法相结合，我们能够将计算量降低1000倍，结果只需几秒钟，而不是几个小时。我们将FMO-DFTB应用于三种不同的GPCR型配基系统。我们的结果与定点突变数据和已发表文献中的发现很好地关联，表明FMO-DFTB是一种快速而准确的GPCR-配体相互作用的方法。(C)2017作者。《计算化学杂志》由威利期刊出版公司出版。
The reliable and precise evaluation of receptor–ligand interactions and pair‐interaction energy is an essential element of rational drug design. While quantum mechanical (QM) methods have been a promising means by which to achieve this, traditional QM is not applicable for large biological systems due to its high computational cost. Here, the fragment molecular orbital (FMO) method has been used to accelerate QM calculations, and by combining FMO with the density‐functional tight‐binding (DFTB) method we are able to decrease computational cost 1000 times, achieving results in seconds, instead of hours. We have applied FMO‐DFTB to three different GPCR–ligand systems. Our results correlate well with site directed mutagenesis data and findings presented in the published literature, demonstrating that FMO‐DFTB is a rapid and accurate means of GPCR–ligand interactions. © 2017 Authors. Journal of Computational Chemistry Published by Wiley Periodicals, Inc.
登录
查看更多内容
使用碎片分子轨道方法研究激动剂 - 蛋白质-2受体相互作用。
影响因子：
3.9
作者：
Heifetz A;Aldeghi M;Chudyk EI;Fedorov DG;Bodkin MJ;Biggin PC
通讯作者：
Biggin PC
影响因子：
5.5
作者：
Gaus, Michael;Goez, Albrecht;Elstner, Marcus
通讯作者：
Elstner, Marcus
人 P2Y(12) 受体与抗血栓药物复合物的结构
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.8
作者：
Wu, Huixian;Wacker, Daniel;Mileni, Mauro;Katritch, Vsevolod;Han, Gye Won;Vardy, Eyal;Liu, Wei;Thompson, Aaron A.;Huang, Xi-Ping;Carroll, F. Ivy;Mascarella, S. Wayne;Westkaemper, Richard B.;Mosier, Philip D.;Roth, Bryan L.;Cherezov, Vadim;Stevens, Raymond C.
通讯作者：
Stevens, Raymond C.
影响因子：
4
作者：
Heifetz, Alexander;James, Tim;Biggin, Philip C.
通讯作者：
Biggin, Philip C.