TY - JOUR
T1 - FastDRH
T2 - A webserver to predict and analyze protein-ligand complexes based on molecular docking and MM/PB(GB)SA computation
AU - Wang, Zhe
AU - Pan, Hong
AU - Sun, Huiyong
AU - Kang, Yu
AU - Liu, Huanxiang
AU - Cao, Dongsheng
AU - Hou, Tingjun
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/9/1
Y1 - 2022/9/1
N2 - Predicting the native or near-native binding pose of a small molecule within a protein binding pocket is an extremely important task in structure-based drug design, especially in the hit-to-lead and lead optimization phases. In this study, fastDRH, a free and open accessed web server, was developed to predict and analyze protein-ligand complex structures. In fastDRH server, AutoDock Vina and AutoDock-GPU docking engines, structure-truncated MM/PB(GB)SA free energy calculation procedures and multiple poses based per-residue energy decomposition analysis were well integrated into a user-friendly and multifunctional online platform. Benefit from the modular architecture, users can flexibly use one or more of three features, including molecular docking, docking pose rescoring and hotspot residue prediction, to obtain the key information clearly based on a result analysis panel supported by 3Dmol.js and Apache ECharts. In terms of protein-ligand binding mode prediction, the integrated structure-truncated MM/PB(GB)SA rescoring procedures exhibit a success rate of >80% in benchmark, which is much better than the AutoDock Vina (~70%). For hotspot residue identification, our multiple poses based per-residue energy decomposition analysis strategy is a more reliable solution than the one using only a single pose, and the performance of our solution has been experimentally validated in several drug discovery projects. To summarize, the fastDRH server is a useful tool for predicting the ligand binding mode and the hotspot residue of protein for ligand binding. The fastDRH server is accessible free of charge at http://cadd.zju.edu.cn/fastdrh/.
AB - Predicting the native or near-native binding pose of a small molecule within a protein binding pocket is an extremely important task in structure-based drug design, especially in the hit-to-lead and lead optimization phases. In this study, fastDRH, a free and open accessed web server, was developed to predict and analyze protein-ligand complex structures. In fastDRH server, AutoDock Vina and AutoDock-GPU docking engines, structure-truncated MM/PB(GB)SA free energy calculation procedures and multiple poses based per-residue energy decomposition analysis were well integrated into a user-friendly and multifunctional online platform. Benefit from the modular architecture, users can flexibly use one or more of three features, including molecular docking, docking pose rescoring and hotspot residue prediction, to obtain the key information clearly based on a result analysis panel supported by 3Dmol.js and Apache ECharts. In terms of protein-ligand binding mode prediction, the integrated structure-truncated MM/PB(GB)SA rescoring procedures exhibit a success rate of >80% in benchmark, which is much better than the AutoDock Vina (~70%). For hotspot residue identification, our multiple poses based per-residue energy decomposition analysis strategy is a more reliable solution than the one using only a single pose, and the performance of our solution has been experimentally validated in several drug discovery projects. To summarize, the fastDRH server is a useful tool for predicting the ligand binding mode and the hotspot residue of protein for ligand binding. The fastDRH server is accessible free of charge at http://cadd.zju.edu.cn/fastdrh/.
KW - MM/PB(GB)SA
KW - hotspot residue
KW - molecular docking
KW - protein-ligand binding mode
KW - webserver
UR - http://www.scopus.com/inward/record.url?scp=85138333947&partnerID=8YFLogxK
U2 - 10.1093/bib/bbac201
DO - 10.1093/bib/bbac201
M3 - Article
C2 - 35580866
AN - SCOPUS:85138333947
SN - 1467-5463
VL - 23
JO - Briefings in Bioinformatics
JF - Briefings in Bioinformatics
IS - 5
M1 - bbac201
ER -