Blind prediction of host–guest binding affinities: a new SAMPL3 challenge

@article{Muddana2012BlindPO,
  title={Blind prediction of host–guest binding affinities: a new SAMPL3 challenge},
  author={Hari S. Muddana and C. Daniel Varnado and Christopher W. Bielawski and Adam R. Urbach and Lyle D Isaacs and Matthew T. Geballe and Michael K. Gilson},
  journal={Journal of Computer-Aided Molecular Design},
  year={2012},
  volume={26},
  pages={475-487}
}
The computational prediction of protein–ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands—i.e., host–guest systems—represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge… 
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TLDR
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SAMPL3: blinded prediction of host–guest binding affinities, hydration free energies, and trypsin inhibitors
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  • Biology
    Journal of Computer-Aided Molecular Design
  • 2012
TLDR
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References

SHOWING 1-10 OF 84 REFERENCES
Host-guest complexes with protein-ligand-like affinities: computational analysis and design.
TLDR
The Mining Minima algorithm is used to computationally test a new series of CB[7] ligands designed to bind with similarly high affinity and reproduce key experimental observations regarding the affinities of ferrocene-based guests with CB[ 7] and beta-cyclodextrin.
Calculation of protein-ligand binding affinities.
TLDR
This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches.
CSAR Benchmark Exercise of 2010: Selection of the Protein–Ligand Complexes
TLDR
The details of how the data set was initially selected, and the process by which it matured to better fit the needs of the community are presented, underscores the value of a supportive, collaborative effort in moving the field forward.
The SAMPL2 blind prediction challenge: introduction and overview
TLDR
The results of this blind assessment of the state of the field for transfer energy and tautomer ratio prediction both indicate where the field is performing well and point out flaws in current methods.
Binding affinities of host-guest, protein-ligand, and protein-transition-state complexes.
TLDR
The origins of the distributions of association constants observed for the broad range of host-guest systems are explored, and typical approaches to compute and analyze host-GUest binding in solution are discussed.
Calculation of cyclodextrin binding affinities: energy, entropy, and implications for drug design.
TLDR
The second generation Mining Minima method yields binding affinities accurate to within 0.8 kcal/mol for the associations of alpha-, beta-, and gamma-cyclodextrin with benzene, resorcinol, flurbiprofen, naproxen, and nabumetone and indicates that the computed entropy changes show a near-linear relationship with the changes in mean potential plus solvation energy.
Recent theoretical and computational advances for modeling protein-ligand binding affinities.
Enzyme/non-enzyme discrimination and prediction of enzyme active site location using charge-based methods.
Docking and scoring in virtual screening for drug discovery: methods and applications
TLDR
Key concepts and specific features of small-molecule–protein docking methods are reviewed, selected applications are highlighted and recent advances that aim to address the acknowledged limitations of established approaches are discussed.
S66: A Well-balanced Database of Benchmark Interaction Energies Relevant to Biomolecular Structures
TLDR
A large new database of interaction energies calculated using an accurate CCSD(T)/CBS scheme is presented, designed to cover the most common types of noncovalent interactions in biomolecules, while keeping a balanced representation of dispersion and electrostatic contributions.
...
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