NMR-Fragment Based Virtual Screening: A Brief Overview

Singh, Meenakshi; Tam, Benjamin; Akabayov, Barak

doi:10.3390/molecules23020233

Cited by 39 publications

(24 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of the increased accuracy of the computationally programs, virtual screening methods have become more common in FBDD [20]. Several recent reviews cover this topic in detail [28,29,30]. Usually, the VS procedure is designed in a project-specific manner to account for the information available on the target and/or already-known ligands.…”

Section: Fragment Hit Identificationmentioning

confidence: 99%

Concepts and Core Principles of Fragment-Based Drug Design

et al. 2019

View full text Add to dashboard Cite

In this review, a general introduction to fragment-based drug design and the underlying concepts is given. General considerations and methodologies ranging from library selection/construction over biophysical screening and evaluation methods to in-depth hit qualification and subsequent optimization strategies are discussed. These principles can be generally applied to most classes of drug targets. The examples given for fragment growing, merging, and linking strategies at the end of the review are set in the fields of enzyme-inhibitor design and macromolecule–macromolecule interaction inhibition. Building upon the foundation of fragment-based drug discovery (FBDD) and its methodologies, we also highlight a few new trends in FBDD.

show abstract

Section: Fragment Hit Identificationmentioning

confidence: 99%

Concepts and Core Principles of Fragment-Based Drug Design

et al. 2019

View full text Add to dashboard Cite

show abstract

“…A potent compound was able to be developed through FBDD in which a library of about 800 fragments was utilized ( Sabbah et al, 2020 ). Quite a few fragment libraries are commercially available ( Singh et al, 2018 ). Many researchers have built up their own fragment libraries based on their respective experience ( Garner et al, 2019 ; Heidrich et al, 2019 ).…”

Section: Fragment Librarymentioning

confidence: 99%

Application of Fragment-Based Drug Discovery to Versatile Targets

2020

Front. Mol. Biosci.

135

View full text Add to dashboard Cite

Fragment-based drug discovery (FBDD) is a powerful method to develop potent smallmolecule compounds starting from fragments binding weakly to targets. As FBDD exhibits several advantages over high-throughput screening campaigns, it becomes an attractive strategy in target-based drug discovery. Many potent compounds/inhibitors of diverse targets have been developed using this approach. Methods used in fragment screening and understanding fragment-binding modes are critical in FBDD. This review elucidates fragment libraries, methods utilized in fragment identification/confirmation, strategies applied in growing the identified fragments into drug-like lead compounds, and applications of FBDD to different targets. As FBDD can be readily carried out through different biophysical and computer-based methods, it will play more important roles in drug discovery.

show abstract

“…In fragment-based drug discovery, both X-ray crystallography and NMR spectroscopy can be utilized to perform fragment screening and identify the fragment binding site. Structures of target-fragment complexes are indispensable for deciding a strategy for fragment growth [16,[55][56][57]. Structural information of target-ligand complexes enables medicinal chemists to understand the structure-activity relationship (SAR) of the developed small molecules [47,58].…”

Section: Structural Biology In Drug Discoverymentioning

confidence: 99%

“…It is well known that there are some obstacles in drug discovery, such as target selection, initial hit identification, lead optimization and efficacies [ 13 , 14 ]. Hit to lead is a critical step in drug discovery and the hits can be achieved from following strategies such as high throughput screening (HTS) [ 15 ], fragment identification [ 16 , 17 ], structure-based drug design [ 18 , 19 , 20 ], artificial intelligence-based drug design [ 21 ], known compounds from the published literature [ 22 ], the repurposing of approved drugs [ 10 , 23 ] and DNA-encoded library screening [ 24 , 25 , 26 ]. Biochemical and cell-based assays are able to evaluate the activity of the identified hits while pan-assay interference compounds (PAINS) may give false positive results in the assay [ 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

Kang

2020

IJMS

View full text Add to dashboard Cite

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design.

show abstract

NMR-Fragment Based Virtual Screening: A Brief Overview

Cited by 39 publications

References 168 publications

Concepts and Core Principles of Fragment-Based Drug Design

Concepts and Core Principles of Fragment-Based Drug Design

Application of Fragment-Based Drug Discovery to Versatile Targets

Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

Contact Info

Product

Resources

About