ArticleJournal of chemical theory and computation2014
Heterogeneous Hydration of p53/MDM2 Complex.
Article in Journal of chemical theory and computation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 26 citations in OpenAlex.
- Markov State Model of Solvent Features Reveals Water Dynamics in Protein-Peptide Binding.The journal of physical chemistry. B · 2023Article
- Coupling Monte Carlo, Variational Implicit Solvation, and Binary Level-Set for Simulations of Biomolecular Binding.Journal of chemical theory and computation · 2021Article
- Heterogeneous Solvation in Distinctive Protein-Protein Interfaces Revealed by Molecular Dynamics Simulations.The journal of physical chemistry. B · 2018Article
- Tailoring the Variational Implicit Solvent Method for New Challenges: Biomolecular Recognition and Assembly.Frontiers in molecular biosciences · 2018Review
- "Martinizing" the Variational Implicit Solvent Method (VISM): Solvation Free Energy for Coarse-Grained Proteins.The journal of physical chemistry. B · 2017Article
- Binding site elucidation and structure guided design of macrocyclic IL-17A antagonists.Scientific reports · 2016Article
- Stochastic level-set variational implicit-solvent approach to solute-solvent interfacial fluctuations.The Journal of chemical physics · 2016Article
- Numerical Treatment of Stokes Solvent Flow and Solute-Solvent Interfacial Dynamics for Nonpolar Molecules.Journal of scientific computing · 2016Article
- A self-consistent phase-field approach to implicit solvation of charged molecules with Poisson-Boltzmann electrostatics.The Journal of chemical physics · 2015Article
- LS-VISM: A software package for analysis of biomolecular solvation.Journal of computational chemistry · 2015Article
- Identification of protein-ligand binding sites by the level-set variational implicit-solvent approach.Journal of chemical theory and computation · 2015Article
- Variational Implicit Solvation with Poisson-Boltzmann Theory.Journal of chemical theory and computation · 2014Article
- STABILITY OF A CYLINDRICAL SOLUTE-SOLVENT INTERFACE: EFFECT OF GEOMETRY, ELECTROSTATICS, AND HYDRODYNAMICS.SIAM journal on applied mathematicsArticle
- DIFFUSED SOLUTE-SOLVENT INTERFACE WITH POISSON-BOLTZMANN ELECTROSTATICS: FREE-ENERGY VARIATION AND SHARP-INTERFACE LIMIT.SIAM journal on applied mathematicsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Water-mediated interactions play critical roles in biomolecular recognition processes. Explicit solvent molecular dynamics (MD) simulations and the variational implicit-solvent model (VISM) are used to study those hydration properties during binding for the biologically important p53/MDM2 complex. Unlike simple model solutes, in such a realistic and heterogeneous solute-solvent system with both geometrical and chemical complexity, the local water distribution sensitively depends on nearby amino acid properties and the geometric shape of the protein. We show that the VISM can accurately describe the locations of high and low density solvation shells identified by the MD simulations and can explain them by a local coupling balance of solvent-solute interaction potentials and curvature. In particular, capillary transitions between local dry and wet hydration states in the binding pocket are captured for interdomain distance between 4 to 6 Å, right at the onset of binding. The underlying physical connection between geometry and polarity is illustrated and quantified. Our study offers a microscopic and physical insight into the heterogeneous hydration behavior of the biologically highly relevant p53/MDM2 system and demonstrates the fundamental importance of hydrophobic effects for biological binding processes. We hope our study can help to establish new design rules for drugs and medical substances.
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.