Structural basis for Kisspeptin-10 selectivity toward KISS1R: computational insights.

Netesa MA, Pyurveev SS, Lebedev AA, Bychkov ER, Skorb EV, Shityakov S, Shabanov PD

In silico pharmacology6 Sept 2026

PMID42707558DOI10.1007/s40203-026-00726-0PepBankPUB-42707558

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

01Computer modelIn silicoActivity measurement
In molecular dynamics simulations, Kisspeptin‑10 had its lowest (most favourable) binding free energy at KISS1R.
In plain wordsIn computer simulations, Kisspeptin‑10 bound its own receptor KISS1R more tightly than the other receptors tested.
Peptide
Kisspeptin-10
Outcome
Not applicableBinding free energy at KISS1R
Study
n: not reported in source
AlphaFold2 receptor models in lipid bilayers, 500-ns MD
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Measurements
Binding free energy (GB)
−158.3 kcal/mol
KISS1R
Source sentences
Summary
Binding free energies calculated via the implicit solvation method revealed the lowest binding energies for KISS1R (ΔG_GB =- 158.3 ± 6.9 kcal/mol), followed by NPFF1R (ΔG_GB =- 155.5 ± 10.0 kcal/mol), with substantially weaker interactions for 5-HT1AR (- 136.5 ± 9.2 kcal/mol), D2…
1 context sentence(design, population, supporting numbers)
Summary · context
Three-dimensional structures of KP-10 bound to kisspeptin receptor 1 (KISS1R), neuropeptide FF receptor 1 (NPFF1R), dopamine D1/D2 receptors (D1R/D2R), and serotonin 5-HT1A/2A receptors (5-HT1AR/5-HT2AR) were predicted via AlphaFold2 and embedded in lipid bilayers for 500-ns molecular dynamics simulations.
Report a problemFND-4270755801
02Computer modelIn silicoActivity measurement
In molecular dynamics simulations, Kisspeptin‑10 had the second lowest binding free energy, at NPFF1R.
In plain wordsIn computer simulations, Kisspeptin‑10 bound the NPFF1 receptor almost as tightly as KISS1R.
Peptide
Kisspeptin-10
Outcome
Not applicableBinding free energy at NPFF1R
Study
n: not reported in source
AlphaFold2 receptor models in lipid bilayers, 500-ns MD
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Measurements
Binding free energy (GB)
−155.5 kcal/mol
NPFF1R
Source sentences
Summary
Binding free energies calculated via the implicit solvation method revealed the lowest binding energies for KISS1R (ΔG_GB =- 158.3 ± 6.9 kcal/mol), followed by NPFF1R (ΔG_GB =- 155.5 ± 10.0 kcal/mol), with substantially weaker interactions for 5-HT1AR (- 136.5 ± 9.2 kcal/mol), D2…
1 context sentence(design, population, supporting numbers)
Summary · context
Three-dimensional structures of KP-10 bound to kisspeptin receptor 1 (KISS1R), neuropeptide FF receptor 1 (NPFF1R), dopamine D1/D2 receptors (D1R/D2R), and serotonin 5-HT1A/2A receptors (5-HT1AR/5-HT2AR) were predicted via AlphaFold2 and embedded in lipid bilayers for 500-ns molecular dynamics simulations.
Report a problemFND-4270755802
03Computer modelIn silicoActivity measurement
In molecular dynamics simulations, Kisspeptin‑10 showed substantially weaker binding at the serotonin 5-HT1A receptor than at KISS1R.
In plain wordsIn computer simulations, Kisspeptin‑10 bound the serotonin 1A receptor much more weakly than KISS1R.
Peptide
Kisspeptin-10
Outcome
Not applicableBinding free energy at 5-HT1AR
Study
n: not reported in source
AlphaFold2 receptor models in lipid bilayers, 500-ns MD
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Measurements
Binding free energy (GB)
−136.5 kcal/mol
5-HT1AR
Source sentences
Summary
Binding free energies calculated via the implicit solvation method revealed the lowest binding energies for KISS1R (ΔG_GB =- 158.3 ± 6.9 kcal/mol), followed by NPFF1R (ΔG_GB =- 155.5 ± 10.0 kcal/mol), with substantially weaker interactions for 5-HT1AR (- 136.5 ± 9.2 kcal/mol), D2…
1 context sentence(design, population, supporting numbers)
Summary · context
Three-dimensional structures of KP-10 bound to kisspeptin receptor 1 (KISS1R), neuropeptide FF receptor 1 (NPFF1R), dopamine D1/D2 receptors (D1R/D2R), and serotonin 5-HT1A/2A receptors (5-HT1AR/5-HT2AR) were predicted via AlphaFold2 and embedded in lipid bilayers for 500-ns molecular dynamics simulations.
Report a problemFND-4270755803
04Computer modelIn silicoActivity measurement
In molecular dynamics simulations, Kisspeptin‑10 showed substantially weaker binding at the dopamine D2 receptor than at KISS1R.
In plain wordsIn computer simulations, Kisspeptin‑10 bound the dopamine D2 receptor much more weakly than KISS1R.
Peptide
Kisspeptin-10
Outcome
Not applicableBinding free energy at D2R
Study
n: not reported in source
AlphaFold2 receptor models in lipid bilayers, 500-ns MD
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Measurements
Binding free energy (GB)
−115.9 kcal/mol
D2R
Source sentences
Summary
Binding free energies calculated via the implicit solvation method revealed the lowest binding energies for KISS1R (ΔG_GB =- 158.3 ± 6.9 kcal/mol), followed by NPFF1R (ΔG_GB =- 155.5 ± 10.0 kcal/mol), with substantially weaker interactions for 5-HT1AR (- 136.5 ± 9.2 kcal/mol), D2…
1 context sentence(design, population, supporting numbers)
Summary · context
Three-dimensional structures of KP-10 bound to kisspeptin receptor 1 (KISS1R), neuropeptide FF receptor 1 (NPFF1R), dopamine D1/D2 receptors (D1R/D2R), and serotonin 5-HT1A/2A receptors (5-HT1AR/5-HT2AR) were predicted via AlphaFold2 and embedded in lipid bilayers for 500-ns molecular dynamics simulations.
Report a problemFND-4270755804
05Computer modelIn silicoActivity measurement
In molecular dynamics simulations, Kisspeptin‑10 showed substantially weaker binding at the serotonin 5-HT2A receptor than at KISS1R.
In plain wordsIn computer simulations, Kisspeptin‑10 bound the serotonin 2A receptor much more weakly than KISS1R.
Peptide
Kisspeptin-10
Outcome
Not applicableBinding free energy at 5-HT2AR
Study
n: not reported in source
AlphaFold2 receptor models in lipid bilayers, 500-ns MD
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Measurements
Binding free energy (GB)
−111.1 kcal/mol
5-HT2AR
Source sentences
Summary
Binding free energies calculated via the implicit solvation method revealed the lowest binding energies for KISS1R (ΔG_GB =- 158.3 ± 6.9 kcal/mol), followed by NPFF1R (ΔG_GB =- 155.5 ± 10.0 kcal/mol), with substantially weaker interactions for 5-HT1AR (- 136.5 ± 9.2 kcal/mol), D2…
1 context sentence(design, population, supporting numbers)
Summary · context
Three-dimensional structures of KP-10 bound to kisspeptin receptor 1 (KISS1R), neuropeptide FF receptor 1 (NPFF1R), dopamine D1/D2 receptors (D1R/D2R), and serotonin 5-HT1A/2A receptors (5-HT1AR/5-HT2AR) were predicted via AlphaFold2 and embedded in lipid bilayers for 500-ns molecular dynamics simulations.
Report a problemFND-4270755805
06Computer modelIn silicoActivity measurement
Conformational stability metrics (RMSD, RMSF, Rg and hydrogen bond occupancy) of the simulated complexes corroborated the binding energy trends.
In plain wordsIn computer simulations, the stability of the Kisspeptin‑10 and receptor complexes matched the binding energy results.
Peptide
Kisspeptin-10
Outcome
Not applicableConformational stability of receptor complexes
Study
n: not reported in source
AlphaFold2 receptor models in lipid bilayers, 500-ns MD
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
Conformational stability metrics (RMSD, RMSF, Rg, and hydrogen bond occupancy) corroborated these energetic trends.
1 context sentence(design, population, supporting numbers)
Summary · context
Three-dimensional structures of KP-10 bound to kisspeptin receptor 1 (KISS1R), neuropeptide FF receptor 1 (NPFF1R), dopamine D1/D2 receptors (D1R/D2R), and serotonin 5-HT1A/2A receptors (5-HT1AR/5-HT2AR) were predicted via AlphaFold2 and embedded in lipid bilayers for 500-ns molecular dynamics simulations.
Report a problemFND-4270755806
07Computer modelIn silicoActivity measurement
The simulations indicated high selectivity of Kisspeptin‑10 for KISS1R compared with dopamine D1/D2 and serotonin 5-HT1A/2A receptors.
In plain wordsComputer simulations suggest Kisspeptin‑10 prefers its own receptor over dopamine and serotonin receptors. Lab confirmation is still needed.
Peptide
Kisspeptin-10
Outcome
Not applicableReceptor selectivity of KP-10
Study
n: not reported in source
AlphaFold2 receptor models in lipid bilayers, 500-ns MD
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
These results demonstrate the high selectivity of KP-10 for KISS1R compared to the following monoaminergic receptors: dopamine types 1 and 2 and serotonin types 1A and 2A, suggesting that its effects on impulsive and compulsive behavior occur primarily through canonical kisspeptin signaling rather t…
1 context sentence(design, population, supporting numbers)
Summary · context
Three-dimensional structures of KP-10 bound to kisspeptin receptor 1 (KISS1R), neuropeptide FF receptor 1 (NPFF1R), dopamine D1/D2 receptors (D1R/D2R), and serotonin 5-HT1A/2A receptors (5-HT1AR/5-HT2AR) were predicted via AlphaFold2 and embedded in lipid bilayers for 500-ns molecular dynamics simulations.
Report a problemFND-4270755807

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 09:43 UTC
Study results updated
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC

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Publication types

Journal Article

Keywords

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