ArticlePLoS computational biology2011
A role for both conformational selection and induced fit in ligand binding by the LAO protein.
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 95 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
95 citing papers in PubMed.
- Role of Hsp70 chaperone in client-protein folding elucidated by Markov state modeling and NMR restraint-assisted molecular dynamics simulations.Biophysical journal · 2026Article
- A continuous-space analytical framework for committor functions from molecular dynamics.The Journal of chemical physics · 2026Article
- Rational design framework for fluorescent biosensors from periplasmic binding proteins.Bioscience reports · 2026Article
- Nucleosome condensate and linker DNA alter chromatin folding pathways and rates.Biophysical journal · 2026Article
- Immunoinformatics approach to engineer a multi-epitope vaccine against SdrG in skin commensal Staphylococcus epidermidis.PloS one · 2026Article
- AMUSET-TICA: A Tensor-Based Approach for Identifying Slow Collective Variables in Biomolecular Dynamics.Journal of chemical theory and computation · 2025Article
- Exploring transition states of protein conformational changes via out-of-distribution detection in the hyperspherical latent space.Nature communications · 2025Article
- Incorporating Prior Knowledge in the Seeds of Adaptive Sampling Molecular Dynamics Simulations of Ligand Transport in Enzymes with Buried Active Sites.Journal of chemical theory and computation · 2024Article
- Molecular dynamics in multidimensional space explains how mutations affect the association path of neomycin to a riboswitch.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Tutorial on how to build non-Markovian dynamic models from molecular dynamics simulations for studying protein conformational changes.The Journal of chemical physics · 2024Article
- A Kinetic Transition Network Model Reveals the Diversity of Protein Dimer Formation Mechanisms.Biomolecules · 2023Article
- Integrative generalized master equation: A method to study long-timescale biomolecular dynamics via the integrals of memory kernels.The Journal of chemical physics · 2023Article
- An Efficient Path Classification Algorithm Based on Variational Autoencoder to Identify Metastable Path Channels for Complex Conformational Changes.Journal of chemical theory and computation · 2023Article
- Folding@home: Achievements from over 20 years of citizen science herald the exascale era.Biophysical journal · 2023Review
- Folding@home: achievements from over twenty years of citizen science herald the exascale era.ArXiv · 2023Article
- Deep learning to decompose macromolecules into independent Markovian domains.Nature communications · 2022Article
- A litmus test for classifying recognition mechanisms of transiently binding proteins.Nature communications · 2022Article
- Computational investigations on target-site searching and recognition mechanisms by thymine DNA glycosylase during DNA repair process.Acta biochimica et biophysica Sinica · 2022Review
- Practical Protocols for Efficient Sampling of Kinase-Inhibitor Binding Pathways Using Two-Dimensional Replica-Exchange Molecular Dynamics.Frontiers in molecular biosciences · 2022Article
- Critical role of backbone coordination in the mRNA recognition by RNA induced silencing complex.Communications biology · 2021Article
35 more citing papers are in PubMed but not listed here.
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.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular recognition is determined by the structure and dynamics of both a protein and its ligand, but it is difficult to directly assess the role of each of these players. In this study, we use Markov State Models (MSMs) built from atomistic simulations to elucidate the mechanism by which the Lysine-, Arginine-, Ornithine-binding (LAO) protein binds to its ligand. We show that our model can predict the bound state, binding free energy, and association rate with reasonable accuracy and then use the model to dissect the binding mechanism. In the past, this binding event has often been assumed to occur via an induced fit mechanism because the protein's binding site is completely closed in the bound state, making it impossible for the ligand to enter the binding site after the protein has adopted the closed conformation. More complex mechanisms have also been hypothesized, but these have remained controversial. Here, we are able to directly observe roles for both the conformational selection and induced fit mechanisms in LAO binding. First, the LAO protein tends to form a partially closed encounter complex via conformational selection (that is, the apo protein can sample this state), though the induced fit mechanism can also play a role here. Then, interactions with the ligand can induce a transition to the bound state. Based on these results, we propose that MSMs built from atomistic simulations may be a powerful way of dissecting ligand-binding mechanisms and may eventually facilitate a deeper understanding of allostery as well as the prediction of new protein-ligand interactions, an important step in drug discovery.
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.