Residue-based pharmacophore approaches to study protein–protein interactions

Shrestha, Rojan; Fajardo, J. Eduardo; Fiser, András

doi:10.1016/j.sbi.2020.12.016

Cited by 6 publications

(6 citation statements)

References 57 publications

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“…The resulting residue‐based pharmacophore (rs‐pharmacophore) comprises the residue types and location preferences on the complementary interface. This rs‐pharmacophore is subsequently used to find potential matches among candidate ligands using a pattern matching algorithm (Shrestha et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

Assessing the functional impact of protein binding site definition

Nandigrami,

Fiser

2024

Protein Science

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Many biomedical applications, such as classification of binding specificities or bioengineering, depend on the accurate definition of protein binding interfaces. Depending on the choice of method used, substantially different sets of residues can be classified as belonging to the interface of a protein. A typical approach used to verify these definitions is to mutate residues and measure the impact of these changes on binding. Besides the lack of exhaustive data, this approach also suffers from the fundamental problem that a mutation introduces an unknown amount of alteration into an interface, which potentially alters the binding characteristics of the interface. In this study we explore the impact of alternative binding site definitions on the ability of a protein to recognize its cognate ligand using a pharmacophore approach, which does not affect the interface. The study also shows that methods for protein binding interface predictions should perform above approximately F‐score = 0.7 accuracy level to capture the biological function of a protein.

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Section: Methodsmentioning

confidence: 99%

Assessing the functional impact of protein binding site definition

Nandigrami,

Fiser

2024

Protein Science

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“…The resulting residue-based pharmacophore (rs-pharmacophore) comprises the residue types and location preferences on the complementary interface. This rs-pharmacophore is subsequently used to find potential matches among candidate ligands using a pattern matching algorithm (41).…”

Section: Methodsmentioning

confidence: 99%

“…The rs-pharmacophore is then used to screen candidate ligands for the given protein receptor where each candidate ligand is ranked according to the degree of match against the predicted rs-pharmacophore. The candidates that are highly ranked are the predicted binding partner(s) of the given protein (41). ProtLID was successfully used to identify the cognate partners for a given receptor (38), and to redesign various protein interfaces for ligand binding specificity (42, 43).…”

Section: Introductionmentioning

confidence: 99%

Assessing the functional impact of protein binding site definition

Nandigrami

Fiser

2023

Preprint

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Many biomedical applications, such as classification of binding specificities or bioengineering, depend on the accurate definition of protein binding interfaces. Depending on the choice of method used, substantially different sets of residues can be classified as belonging to the interface of a protein. A typical approach used to verify these definitions is to mutate residues and measure the impact of these changes on binding. Besides the lack of exhaustive data this approach generates, it also suffers from the fundamental problem that a mutation introduces an unknown amount of alteration into an interface, which potentially alters the binding characteristics of the interface. In this study we explore the impact of alternative binding site definitions on the ability of a protein to recognize its cognate ligand using a pharmacophore approach, which does not affect the interface. The study also provides guidance on the minimum expected accuracy of interface definition that is required to capture the biological function of a protein.

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“…Docking-based virtual screening has been widely used in drug discovery due to its efficiency and convenience . However, most of the existing docking software ignores the flexibility of the protein, which leads to the crash between the potential active compounds and the binding pocket. , Pharmacophore model uses the pharmacophore features to characterize the elements necessary for the ligand to bind with the target protein regardless of the actual binding mode, which actually takes into account the flexibility changes of target proteins . In our previous work, an integrated screening scheme coupling pharmacophore-based screening with molecular docking was successfully employed to discover cyclic D -peptide NKTP-3 for lung cancer treatment .…”

Section: Introductionmentioning

confidence: 99%

Discovery of a Dual Tubulin and Neuropilin-1 (NRP1) Inhibitor with Potent In Vivo Anti-Tumor Activity via Pharmacophore-based Docking Screening, Structure Optimization, and Biological Evaluation

Zheng,

Zou,

Xie

et al. 2023

J. Med. Chem.

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Residue-based pharmacophore approaches to study protein–protein interactions

Cited by 6 publications

References 57 publications

Assessing the functional impact of protein binding site definition

Assessing the functional impact of protein binding site definition

Assessing the functional impact of protein binding site definition

Discovery of a Dual Tubulin and Neuropilin-1 (NRP1) Inhibitor with Potent In Vivo Anti-Tumor Activity via Pharmacophore-based Docking Screening, Structure Optimization, and Biological Evaluation

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