AMMOS2: a web server for protein–ligand–water complexes refinement via molecular mechanics

@article{Labb2017AMMOS2AW,
  title={AMMOS2: a web server for protein–ligand–water complexes refinement via molecular mechanics},
  author={C{\'e}line M. Labb{\'e} and Tania Pencheva and Dessislava Jereva and Dimitri Desvillechabrol and J{\'e}r{\^o}me B{\'e}cot and Bruno O. Villoutreix and Ilza Pajeva and Maria A. Miteva},
  journal={Nucleic Acids Research},
  year={2017},
  volume={45},
  pages={W350 - W355}
}
Abstract AMMOS2 is an interactive web server for efficient computational refinement of protein–small organic molecule complexes. The AMMOS2 protocol employs atomic-level energy minimization of a large number of experimental or modeled protein–ligand complexes. The web server is based on the previously developed standalone software AMMOS (Automatic Molecular Mechanics Optimization for in silico Screening). AMMOS utilizes the physics-based force field AMMP sp4 and performs optimization of protein… 

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References

SHOWING 1-10 OF 42 REFERENCES
AMMOS: Automated Molecular Mechanics Optimization tool for in silico Screening
TLDR
The enrichment study suggests that AMMOS, designed to minimize a large number of ligands pre-docked in a protein target, can successfully be applied in a final post-processing step and that it can take into account some receptor flexibility within the binding site area.
PLIP: fully automated protein–ligand interaction profiler
TLDR
The protein-ligand interaction profiler (PLIP) is presented, a novel web service for fully automated detection and visualization of relevant non-covalent protein–ligand contacts in 3D structures, freely available at projects.tu-dresden.de/plip-web.
CSM-lig: a web server for assessing and comparing protein–small molecule affinities
TLDR
CSM-lig is presented, a web server tailored to predict the binding affinity of a protein-small molecule complex, encompassing both protein and small-molecule complementarity in terms of shape and chemistry via graph-based structural signatures, which would be an invaluable tool for helping assess docking poses.
Energetics of displacing water molecules from protein binding sites: consequences for ligand optimization.
TLDR
Free-energy perturbation calculations were carried out in the context of Monte Carlo statistical mechanics simulations to investigate ligand series that feature displacement of ordered water molecules in the binding sites of scytalone dehydratase, p38-alphaMAP kinase, and EGFR kinase.
Intuitive, but not simple: Including explicit water molecules in protein–protein docking simulations improves model quality
TLDR
The Hydropathic INTeractions (HINT) force field model was used for scoring docked models in a data set of 30 high‐resolution crystallographically characterized “dry” protein–protein complexes and was shown to reliably identify native‐like models.
SwissDock, a protein-small molecule docking web service based on EADock DSS
TLDR
SwissDock, a web server dedicated to the docking of small molecules on target proteins, is presented, based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files.
Thermodynamics of buried water clusters at a protein-ligand binding interface.
TLDR
The calculations reveal that the rearrangement of the water molecules contributes favorably to the binding affinity, even though one of them is displaced going from ligand 1 to 2, leading to a lower binding affinity of ligand 2.
3Drefine: an interactive web server for efficient protein structure refinement
TLDR
The 3Drefine refinement protocol utilizes iterative optimization of hydrogen bonding network combined with atomic-level energy minimization on the optimized model using a composite physics and knowledge-based force fields for efficient protein structure refinement.
KoBaMIN: a knowledge-based minimization web server for protein structure refinement
TLDR
The KoBaMIN web server provides an online interface to a simple, consistent and computationally efficient protein structure refinement protocol based on minimization of a knowledge-based potential of mean force, yielding consistently good results across a broad range of model quality values.
The role of water molecules in computational drug design.
TLDR
This review discusses their influence on the binding process between biomacromolecular targets and small molecule ligands and how this influence can be modeled in computational drug design approaches.
...
...