TWN-RENCOD: A novel method for protein binding site comparison

Choi, Kwang-Eun; Balupuri, Anand; Kang, Nam Sook

doi:10.1016/j.csbj.2022.12.014

Cited by 4 publications

(5 citation statements)

References 46 publications

(90 reference statements)

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“…Histograms No 2022 BindSiteS-CNN [27]a TOUGH-C1, ProSPECCTs without the ROCS Structures data set Ligand or SURFNET [28] Surface Graph No 2023 TWN-RENCOD [29]b Developer-built kinase data set Ligand Residues Matrix No…”

Section: Residuesmentioning

confidence: 99%

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SiteMine: Large‐scale binding site similarity searching in protein structure databases

Reim,

Ehrt,

Graef

et al. 2024

Archiv der Pharmazie

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Drug discovery and design challenges, such as drug repurposing, analyzing protein–ligand and protein–protein complexes, ligand promiscuity studies, or function prediction, can be addressed by protein binding site similarity analysis. Although numerous tools exist, they all have individual strengths and drawbacks with regard to run time, provision of structure superpositions, and applicability to diverse application domains. Here, we introduce SiteMine, an all‐in‐one database‐driven, alignment‐providing binding site similarity search tool to tackle the most pressing challenges of binding site comparison. The performance of SiteMine is evaluated on the ProSPECCTs benchmark, showing a promising performance on most of the data sets. The method performs convincingly regarding all quality criteria for reliable binding site comparison, offering a novel state‐of‐the‐art approach for structure‐based molecular design based on binding site comparisons. In a SiteMine showcase, we discuss the high structural similarity between cathepsin L and calpain 1 binding sites and give an outlook on the impact of this finding on structure‐based drug design. SiteMine is available at https://uhh.de/naomi.

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Section: Residuesmentioning

confidence: 99%

“…TWN‐RENCOD uses topological water networks obtained by short molecular dynamics simulations. [ 29 ] The aqueous environment in binding sites from these simulations is compared. The method was evaluated on a kinase data set comprising only 36 binding site pairs.…”

Section: Introductionmentioning

confidence: 99%

SiteMine: Large‐scale binding site similarity searching in protein structure databases

Reim,

Ehrt,

Graef

et al. 2024

Archiv der Pharmazie

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“…The three-dimensional (3D) structure of proteins is of utmost significance to understand the biological functions of proteins [ 40 ]. Comparing the binding sites of various proteins offers valuable insights into the process of drug discovery and development.…”

Section: Binding Site Comparisonmentioning

confidence: 99%

“…Comparing the binding sites of various proteins offers valuable insights into the process of drug discovery and development. Such comparisons can aid in understanding polypharmacology, identifying potential off-targets, and repurposing existing drugs [ 40 ]. A variety of computational techniques exist to assess protein structures for tackling diverse scientific challenges [ 41 , 42 ].…”

Section: Binding Site Comparisonmentioning

confidence: 99%

An Intriguing Purview on the Design of Macrocyclic Inhibitors for Unexplored Protein Kinases through Their Binding Site Comparison

Bhujbal

Hah

2023

Pharmaceuticals

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Kinases play an important role in regulating various intracellular signaling pathways that control cell proliferation, differentiation, survival, and other cellular processes, and their deregulation causes more than 400 diseases. Consequently, macrocyclization can be considered a noteworthy approach to developing new therapeutic agents for human diseases. Macrocyclization has emerged as an effective drug discovery strategy over the past decade to improve target selectivity and potency of small molecules. Small compounds with linear structures upon macrocyclization can lead to changes in their physicochemical and biological properties by firmly reducing conformational flexibility. A number of distinct protein kinases exhibit similar binding sites. Comparison of protein binding sites provides crucial insights for drug discovery and development. Binding site similarities are helpful in understanding polypharmacology, identifying potential off-targets, and repurposing known drugs. In this review, we focused on comparing the binding sites of those kinases for which macrocyclic inhibitors are available/studied so far. Furthermore, we calculated the volume of the binding site pocket for each targeted kinase and then compared it with the binding site pocket of the kinase for which only acyclic inhibitors were designed to date. Our review and analysis of several explored kinases might be useful in targeting new protein kinases for macrocyclic drug discovery.

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“…We effectively applied this method for various applications including designing experimentally validated kinase inhibitors [27] , [28] , [29] , studying kinase selectivity [30] , analyzing protein-ligand binding [27] , exploring drug repurposing [31] , [32] , investigating protein hydration [33] and gaining insights into protein folding [34] . Furthermore, we introduced a TWN-based residue encoding (TWN-RENCOD) method for comparing protein binding sites that takes into account the distances between TWNs and binding site residues to calculate the similarity between protein binding sites [35] .…”

Section: Introductionmentioning

confidence: 99%

TWN-FS method: A novel fragment screening method for drug discovery

Yoon,

Park,

Balupuri

et al. 2023

Computational and Structural Biotechnology Journal

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TWN-RENCOD: A novel method for protein binding site comparison

Cited by 4 publications

References 46 publications

SiteMine: Large‐scale binding site similarity searching in protein structure databases

SiteMine: Large‐scale binding site similarity searching in protein structure databases

An Intriguing Purview on the Design of Macrocyclic Inhibitors for Unexplored Protein Kinases through Their Binding Site Comparison

TWN-FS method: A novel fragment screening method for drug discovery

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