ArticlePLoS computational biology2011
The free energy landscape of small molecule unbinding.
Article in PLoS computational biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed.
- Hold on tight: the kinetic profiling of opioid receptor ligands using the CORAL-MD.Journal of cheminformatics · 2026Article
- Pharmacological and Computational Insights Into the Analgesic, Antipyretic, and Antidiarrheal Potential ofTheScientificWorldJournal · 2026Article
- Residence time in drug discovery: current insights and future perspectives.Pharmacological reports : PR · 2025Review
- Computational Methodologies in Synthesis, Preparation and Application of Antimicrobial Polymers, Biomolecules, and Nanocomposites.Polymers · 2024Review
- Enhancing SILCS-MC via GPU Acceleration and Ligand Conformational Optimization with Genetic and Parallel Tempering Algorithms.The journal of physical chemistry. B · 2024Article
- Calculating Protein-Ligand Residence Times through State Predictive Information Bottleneck Based Enhanced Sampling.Journal of chemical theory and computation · 2024Article
- Calculating Protein-Ligand Residence Times Through State Predictive Information Bottleneck based Enhanced Sampling.bioRxiv : the preprint server for biology · 2024Article
- Assessment ofCurrent research in structural biology · 2024Article
- Machine learning methods for developments of binding kinetic models in predicting protein-ligand dissociation rate constants.Smart molecules : open access · 2023Article
- Application of Computational Biology and Artificial Intelligence in Drug Design.International journal of molecular sciences · 2022Review
- SEEKR2: Versatile Multiscale Milestoning Utilizing the OpenMM Molecular Dynamics Engine.Journal of chemical information and modeling · 2022Article
- Combined Free-Energy Calculation and Machine Learning Methods for Understanding Ligand Unbinding Kinetics.Journal of chemical theory and computation · 2022Article
- From Data to Knowledge: Systematic Review of Tools for Automatic Analysis of Molecular Dynamics Output.Frontiers in pharmacology · 2022Review
- Creating Maps of the Ligand Binding Landscape for Kinetics-Based Drug Discovery.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Antipyretic activity ofSaudi journal of biological sciences · 2021Article
- Deciphering the Agonist Binding Mechanism to the Adenosine A1 Receptor.ACS pharmacology & translational science · 2021Article
- Antidepressant, anxiolytic, antipyretic, and thrombolytic profiling of methanol extract of the aerial part ofFood science & nutrition · 2021Article
- An Updated Review of Computer-Aided Drug Design and Its Application to COVID-19.BioMed research international · 2021Review
- Protein storytelling through physics.Science (New York, N.Y.) · 2020Review
- Rapid prediction of crucial hotspot interactions for icosahedral viral capsid self-assembly by energy landscape atlasing validated by mutagenesis.PLoS computational biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spontaneous dissociation of six small ligands from the active site of FKBP (the FK506 binding protein) is investigated by explicit water molecular dynamics simulations and network analysis. The ligands have between four (dimethylsulphoxide) and eleven (5-diethylamino-2-pentanone) non-hydrogen atoms, and an affinity for FKBP ranging from 20 to 0.2 mM. The conformations of the FKBP/ligand complex saved along multiple trajectories (50 runs at 310 K for each ligand) are grouped according to a set of intermolecular distances into nodes of a network, and the direct transitions between them are the links. The network analysis reveals that the bound state consists of several subbasins, i.e., binding modes characterized by distinct intermolecular hydrogen bonds and hydrophobic contacts. The dissociation kinetics show a simple (i.e., single-exponential) time dependence because the unbinding barrier is much higher than the barriers between subbasins in the bound state. The unbinding transition state is made up of heterogeneous positions and orientations of the ligand in the FKBP active site, which correspond to multiple pathways of dissociation. For the six small ligands of FKBP, the weaker the binding affinity the closer to the bound state (along the intermolecular distance) are the transition state structures, which is a new manifestation of Hammond behavior. Experimental approaches to the study of fragment binding to proteins have limitations in temporal and spatial resolution. Our network analysis of the unbinding simulations of small inhibitors from an enzyme paints a clear picture of the free energy landscape (both thermodynamics and kinetics) of ligand unbinding.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.