PMID- 33724276
OWN - NLM
STAT- MEDLINE
DCOM- 20210712
LR  - 20210712
IS  - 1463-9084 (Electronic)
IS  - 1463-9076 (Linking)
VI  - 23
IP  - 11
DP  - 2021 Mar 21
TI  - Reinforcement learning to boost molecular docking upon protein conformational 
      ensemble.
PG  - 6800-6806
LID - 10.1039/d0cp06378a [doi]
AB  - Intrinsically disordered proteins (IDPs) are widely involved in human diseases 
      and thus are attractive therapeutic targets. In practice, however, it is 
      computationally prohibitive to dock large ligand libraries to thousands and tens 
      of thousands of conformations. Here, we propose a reversible upper confidence 
      bound (UCB) algorithm for the virtual screening of IDPs to address the influence 
      of the conformation ensemble. The docking process is dynamically arranged so that 
      attempts are focused near the boundary to separate top ligands from the bulk 
      accurately. It is demonstrated in the example of transcription factor c-Myc that 
      the average docking number per ligand can be greatly reduced while the 
      performance is merely slightly affected. This study suggests that reinforcement 
      learning is highly efficient in solving the bottleneck of virtual screening due 
      to the conformation ensemble in the rational drug design of IDPs.
FAU - Chong, Bin
AU  - Chong B
AD  - College of Chemistry and Molecular Engineering, and Beijing National Laboratory 
      for Molecular Sciences (BNLMS), Peking University, Beijing 100871, China. 
      LiuZhiRong@pku.edu.cn.
FAU - Yang, Yingguang
AU  - Yang Y
FAU - Wang, Zi-Le
AU  - Wang ZL
FAU - Xing, Han
AU  - Xing H
FAU - Liu, Zhirong
AU  - Liu Z
LA  - eng
PT  - Journal Article
DEP - 20210316
PL  - England
TA  - Phys Chem Chem Phys
JT  - Physical chemistry chemical physics : PCCP
JID - 100888160
RN  - 0 (Ligands)
RN  - 0 (Proto-Oncogene Proteins c-myc)
SB  - IM
MH  - Algorithms
MH  - Area Under Curve
MH  - Drug Design
MH  - Humans
MH  - Ligands
MH  - *Molecular Docking Simulation
MH  - Protein Binding
MH  - Protein Conformation
MH  - Proto-Oncogene Proteins c-myc/*chemistry/metabolism
MH  - ROC Curve
EDAT- 2021/03/17 06:00
MHDA- 2021/07/13 06:00
CRDT- 2021/03/16 12:32
PHST- 2021/03/17 06:00 [pubmed]
PHST- 2021/07/13 06:00 [medline]
PHST- 2021/03/16 12:32 [entrez]
AID - 10.1039/d0cp06378a [doi]
PST - ppublish
SO  - Phys Chem Chem Phys. 2021 Mar 21;23(11):6800-6806. doi: 10.1039/d0cp06378a. Epub 
      2021 Mar 16.