期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 27, 期 11, 页码 2253-2260出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.04.010
关键词
RNA; Nucleic acid structure; Small molecule; Computational analysis; Ligandability
资金
- Intramural Research Program of the National Institutes of Health, Center for Cancer Research
- National Cancer Institute (NCI), National Institutes of Health [1 ZIA BC011585 04]
- NATIONAL CANCER INSTITUTE [ZIABC011585] Funding Source: NIH RePORTER
RNA has attracted considerable attention as a target for small molecules. However, methods to identify, study, and characterize suitable RNA targets have lagged behind strategies for protein targets. One approach that has received considerable attention for protein targets has been to utilize computational analysis to investigate ligandable pockets on proteins that are amenable to small molecule binding. These studies have shown that selected physical properties of pockets are important parameters that govern the ability of a structure to bind to small molecules. This work describes a similar analysis to study pockets on all RNAs in the Protein Data Bank (PDB). Using parameters such as buriedness, hydrophobicity, volume, and other properties, the set of all RNAs is analyzed and compared to all proteins. Considerable overlap is observed between the properties of pockets on RNAs and proteins. Thus, many RNAs are capable of populating conformations with pockets that are likely suitable for small molecule binding. Further, principal moment of inertia (PMI) calculations reveal that liganded RNAs exist in diverse structural space, much of which overlaps with protein structural space. Taken together, these results suggest that complex folded RNAs adopt unique structures with pockets that may represent viable opportunities for small molecule targeting.
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