No free energy lunch

@article{Shoichet2007NoFE,
  title={No free energy lunch},
  author={Brian K. Shoichet},
  journal={Nature Biotechnology},
  year={2007},
  volume={25},
  pages={1109-1110}
}
  • B. Shoichet
  • Published 1 October 2007
  • Biology
  • Nature Biotechnology
Prediction of a protein's affinity for a ligand has been improved through fundamental physical modeling. 
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shoichetlab.compbio.ucsf.edu
10 Citations
Background Citations
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10 Citations

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Citation Type

A systematic analysis of atomic protein–ligand interactions in the PDB
We compiled a list of 11 016 unique structures of small-molecule ligands bound to proteins representing 750 873 protein–ligand atomic interactions, and analyzed the frequency, geometry and the impact…
A Systematic Analysis of Atomic Protein-Ligand Interactions in the PDB
TLDR
A list of 11,016 unique structures of small-molecule ligands bound to proteins – 6,444 of which have experimental binding affinity - representing 750,873 protein-ligand atomic interactions is compiled, and the frequency, geometry and impact of each interaction type are analyzed.
Rapid Context-Dependent Ligand Desolvation in Molecular Docking
TLDR
This work relates the Generalized-Born effective Born radii for every ligand atom to a fractional desolvation and uses this fraction to scale an atom-by-atom decomposition of the full transfer free energy.
Systematic analysis of the interactions driving small molecule-RNA recognition.
TLDR
This study examined the Protein Data Bank to highlight privileged interactions underlying small molecule-RNA recognition, and finds that RNA recognition is driven mostly by stacking and hydrogen bonding interactions, while protein recognition is instead driven by hydrophobic effects.
Multiscale molecular dynamics of protein aggregation.
TLDR
It is shown that a smart alternative to brute force and massive computation of uninteresting regions in the all atom potential energy surface is the consideration of a simplified reference potential, explored thoroughly in the relevant regions, combined with a free energy perturbation approach that transforms this simple representation to a full atom representation.
Implicit solvent methods for free energy estimation.
Protein conformational switches: from nature to design.
TLDR
The purpose is to highlight examples that can potentially serve as platforms for the design of custom switches, and focuses on inducible conformational changes that are substantial enough to produce a functional response, yet are relatively simple, structurally well-characterized, and amenable to protein engineering efforts.
Recent trends and applications in 3D virtual screening.
TLDR
It is proposed that the best way to advance the state of the art in 3D VS is to integrate complementary strategies in a single drug discovery pipeline, rather than to focus only on theoretical or computational improvements of individual techniques.
Intimate connections: Inositol pyrophosphates at the interface of metabolic regulation and cell signaling
  • S. Shears
  • Biology
    Journal of cellular physiology
  • 2018
TLDR
This review pursues the idea that many of the biological effects of inositol pyrophosphates can be rationalized by their actions at the interface of cell signaling and metabolism that is essential to cellular and organismal homeostasis.
Identification of lead inhibitors of TMPRSS2 isoform 1 of SARS-CoV-2 target using neural network, random forest, and molecular docking

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