SCORING FUNCTION;
DRUG DISCOVERY;
PREDICTION;
NNSCORE;
PAIRS;
D O I:
10.1021/acs.jcim.6b00355
中图分类号:
R914 [药物化学];
学科分类号:
100701 ;
摘要:
In this work, we propose a deep learning approach to improve docking-based virtual screening. The deep neural network that is introduced, DeepVS, uses the output of a docking program and learns how to extract relevant features from basic data such as atom and residues types obtained from protein ligand complexes. Our approach introduces the use of atom and amino acid embeddings and implements an effective way of creating distributed vector representations of protein ligand complexes by modeling the compound as a set of atom contexts that is further processed by a convolutional layer. One of the main advantages of the proposed method is that it does not require feature engineering. We evaluate DeepVS on the Directory of Useful Decoys (DUD), using the output of two docking programs: Autodock Vina1.1.2 and Dock 6.6. Using a strict evaluation with leave-one-out cross-validation, DeepVS outperforms the docking programs, with regard to both AUC ROC and enrichment factor. Moreover, using the output of Autodock DeepVS achieves, an AUC ROC of 0.81, which, to the best of our knowledge, is the best AUC reported so far for virtual screening using the 40 receptors from the DUD.
机构:
Meton AI Inc, Wilmington, DE 19801 USA
Univ Austral, Austral Inst Appl Artifcial Intelligence, Pilar, Buenos Aires, ArgentinaMeton AI Inc, Wilmington, DE 19801 USA
Scardino, Valeria
Bollini, Mariela
论文数: 0引用数: 0
h-index: 0
机构:
Consejo Nacl Invest Cient & Tecn, Ctr Invest BioNanociencias CIBION, Pilar, Buenos Aires, ArgentinaMeton AI Inc, Wilmington, DE 19801 USA
Bollini, Mariela
Cavasotto, Claudio N.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Austral, Austral Inst Appl Artifcial Intelligence, Pilar, Buenos Aires, Argentina
Univ Austral, CONICET, Inst Invest Med Traslac IIMT, Computat Drug Design & Biomed Informat Lab, Pilar, Buenos Aires, Argentina
Univ Austral, Fac Ciencias Biomed, Pilar, Buenos Aires, ArgentinaMeton AI Inc, Wilmington, DE 19801 USA
机构:
Nanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
Xiong, Fengmin
Ding, Xiaoyu
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
Ding, Xiaoyu
Zhang, Hao
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
Zhang, Hao
Luo, Xiaomin
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
Luo, Xiaomin
Chen, Kaixian
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
Chen, Kaixian
Jiang, Hualiang
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R China
UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
Jiang, Hualiang
Luo, Cheng
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
Univ Chinese Acad Sci, Beijing 100049, Peoples R China
UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China
Luo, Cheng
Xu, Heng
论文数: 0引用数: 0
h-index: 0
机构:
Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R ChinaNanchang Univ, Sch Pharm, Nanchang 330006, Jiangxi, Peoples R China