ArticleBiophysical journal2011
Mechanisms of protein-ligand association and its modulation by protein mutations.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 76 citations in OpenAlex.
- Dynamics-informed multigraph neural networks for protein thermostability prediction and residue-level interpretation.iScience · 2026Article
- Toosendanin suppresses acute myeloid leukemia by targeting DDX5/c-Myc axis to inhibit protein synthesis.Journal of translational medicine · 2026Article
- Structural and functional analysis of theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unveiling the Conformational Dynamics of the Histone Tails Using Markov State Modeling.Journal of chemical theory and computation · 2025Article
- Decoding the effects of mutation on protein interactions using machine learning.Biophysics reviews · 2025Review
- Dynamics of receptor activation by agonists.Biophysical journal · 2024Review
- Identification of a Cryptic Pocket in Methionine Aminopeptidase-II Using Adaptive Bandit Molecular Dynamics Simulations and Markov State Models.ACS omega · 2024Article
- Diffusion-Controlled Reactions: An Overview.Molecules (Basel, Switzerland) · 2023Review
- Article
- GraphVAMPNet, using graph neural networks and variational approach to Markov processes for dynamical modeling of biomolecules.The Journal of chemical physics · 2022Article
- Homology Modeling,Frontiers in cellular and infection microbiology · 2022Article
- Impact of crowded environments on binding between protein and single-stranded DNA.Scientific reports · 2021Article
- Combined Linear Interaction Energy and Alchemical Solvation Free-Energy Approach for Protein-Binding Affinity Computation.Journal of chemical theory and computation · 2020Article
- Homology models of mouse and rat estrogen receptor-Computational toxicology (Amsterdam, Netherlands) · 2019Article
- Rate Constants and Mechanisms of Protein-Ligand Binding.Annual review of biophysics · 2017Review
- Protein-ligand (un)binding kinetics as a new paradigm for drug discovery at the crossroad between experiments and modelling.MedChemComm · 2017Review
- Kinetics of O2 Entry and Exit in Monomeric Sarcosine Oxidase via Markovian Milestoning Molecular Dynamics.Journal of chemical theory and computation · 2016Article
- Principles and Overview of Sampling Methods for Modeling Macromolecular Structure and Dynamics.PLoS computational biology · 2016Review
- Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods.International journal of molecular sciences · 2016Review
- Exploration of gated ligand binding recognizes an allosteric site for blocking FABP4-protein interaction.Physical chemistry chemical physics : PCCP · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-ligand interactions are essential for nearly all biological processes, and yet the biophysical mechanism that enables potential binding partners to associate before specific binding occurs remains poorly understood. Fundamental questions include which factors influence the formation of protein-ligand encounter complexes, and whether designated association pathways exist. To address these questions, we developed a computational approach to systematically analyze the complete ensemble of association pathways. Here, we use this approach to study the binding of a phosphate ion to the Escherichia coli phosphate-binding protein. Various mutants of the protein are considered, and their effects on binding free-energy profiles, association rates, and association pathway distributions are quantified. The results reveal the existence of two anion attractors, i.e., regions that initially attract negatively charged particles and allow them to be efficiently screened for phosphate, which is subsequently specifically bound. Point mutations that affect the charge on these attractors modulate their attraction strength and speed up association to a factor of 10 of the diffusion limit, and thus change the association pathways of the phosphate ligand. It is demonstrated that a phosphate that prebinds to such an attractor neutralizes its attraction effect to the environment, making the simultaneous association of a second phosphate ion unlikely. This study suggests ways in which structural properties can be used to tune molecular association kinetics so as to optimize the efficiency of binding, and highlights the importance of kinetic properties.
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.