ArticleBiophysical journal2017
Multiple Ligand Unbinding Pathways and Ligand-Induced Destabilization Revealed by WExplore.
Article in Biophysical journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 86 citations in OpenAlex.
- A theoretical framework for random acceleration molecular dynamics simulations.The Journal of chemical physics · 2026Article
- Reinforcing Tunnel Network Exploration in Proteins Using Gaussian Accelerated Molecular Dynamics.Journal of chemical information and modeling · 2024Article
- Machine learning methods for developments of binding kinetic models in predicting protein-ligand dissociation rate constants.Smart molecules : open access · 2023Article
- How Robust Is the Ligand Binding Transition State?Journal of the American Chemical Society · 2023Article
- Perspectives on Ligand/Protein Binding Kinetics Simulations: Force Fields, Machine Learning, Sampling, and User-Friendliness.Journal of chemical theory and computation · 2023Review
- OneOPES, a Combined Enhanced Sampling Method to Rule Them All.Journal of chemical theory and computation · 2023Article
- Uncovering the Kinetic Characteristics and Degradation Preference of PROTAC Systems with Advanced Theoretical Analyses.JACS Au · 2023Article
- Water regulates the residence time of Benzamidine in Trypsin.Nature communications · 2022Article
- Protein Flexibility and Dissociation Pathway Differentiation Can Explain Onset of Resistance Mutations in Kinases.Angewandte Chemie (International ed. in English) · 2022Article
- Enhanced-Sampling Simulations for the Estimation of Ligand Binding Kinetics: Current Status and Perspective.Frontiers in molecular biosciences · 2022Review
- Local Ion Densities can Influence Transition Paths of Molecular Binding.Frontiers in molecular biosciences · 2022Article
- Metadynamics-Based Approaches for Modeling the Hypoxia-Inducible Factor 2α Ligand Binding Process.Journal of chemical theory and computation · 2021Article
- Pepsin-like aspartic proteases (PAPs) as model systems for combining biomolecular simulation with biophysical experiments.RSC advances · 2021Review
- Molecular dynamics simulations of ortho-carborane nano-diamond storage within the nonpolar channel cavities of a right-handed coiled-coil tetrabrachion nanotube.Computational and structural biotechnology journal · 2021Article
- Wepy: A Flexible Software Framework for Simulating Rare Events with Weighted Ensemble Resampling.ACS omega · 2020Article
- Thermodynamics and Kinetics of Drug-Target Binding by Molecular Simulation.Chemical reviews · 2020Review
- Enhanced Jarzynski free energy calculations using weighted ensemble.The Journal of chemical physics · 2020Article
- Ligand Gaussian Accelerated Molecular Dynamics (LiGaMD): Characterization of Ligand Binding Thermodynamics and Kinetics.Journal of chemical theory and computation · 2020Article
- Identification of Druggable Kinase Target Conformations Using Markov Model Metastable States Analysis of apo-Abl.Journal of chemical theory and computation · 2020Article
- On Calculating Free Energy Differences Using Ensembles of Transition Paths.Frontiers in molecular biosciences · 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 at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report simulations of full ligand exit pathways for the trypsin-benzamidine system, generated using the sampling technique WExplore. WExplore is able to observe millisecond-scale unbinding events using many nanosecond-scale trajectories that are run without introducing biasing forces. The algorithm generates rare events by dividing the coordinate space into regions, on-the-fly, and balancing computational effort between regions through cloning and merging steps, as in the weighted ensemble method. The averaged exit flux yields a ligand exit rate of 180 μs, which is within an order of magnitude of the experimental value. We obtain broad sampling of ligand exit pathways, and visualize our findings using conformation space networks. The analysis shows three distinct exit channels, two of which are formed through large, rare motions of the loop regions in trypsin. This broad set of ligand-bound poses is then used to investigate general properties of ligand binding: we observe both a direct stabilizing effect of ligand-protein interactions and an indirect destabilizing effect on intraprotein interactions that is induced by the ligand. Significantly, the crystallographic binding poses are distinguished not only because their ligands induce large stabilizing effects, but also because they induce relatively low indirect destabilizations.
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.