Expanding molecular modeling and design tools to non‐natural sidechains

@article{Gfeller2012ExpandingMM,
  title={Expanding molecular modeling and design tools to non‐natural sidechains},
  author={David Gfeller and Olivier Michielin and Vincent Zoete},
  journal={Journal of Computational Chemistry},
  year={2012},
  volume={33}
}
Protein–protein interactions encode the wiring diagram of cellular signaling pathways and their deregulations underlie a variety of diseases, such as cancer. Inhibiting protein–protein interactions with peptide derivatives is a promising way to develop new biological and therapeutic tools. Here, we develop a general framework to computationally handle hundreds of non‐natural amino acid sidechains and predict the effect of inserting them into peptides or proteins. We first generate all… 

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References

SHOWING 1-10 OF 61 REFERENCES

Improved prediction of protein side‐chain conformations with SCWRL4

Accuracies as a function of electron density of the side chains demonstrate that side chains with higher electron density are easier to predict than those with low‐electron density and presumed conformational disorder.

SwissParam: A fast force field generation tool for small organic molecules

A fast force field generation tool, called SwissParam, able to generate, for arbitrary small organic molecule, topologies, and parameters based on the Merck molecular force field, but in a functional form that is compatible with the CHARMM force field is presented.

Design of cyclic peptides that bind protein surfaces with antibody-like affinity.

This work describes cyclic messenger RNA display with a trillion-member covalent peptide macrocycle library, and designs a number of high-affinity, redox-insensitive, cyclic peptides that target the signaling protein G alpha i1.

The multiple-specificity landscape of modular peptide recognition domains

It is shown that multiple specificity more accurately predicts protein interactions and experimentally validate some of the predictions for the human proteins DLG1 and SCRIB, suggesting new ways of encoding specificity in protein interaction networks.

CHARMM: The biomolecular simulation program

An overview of the CHARMM program as it exists today is provided with an emphasis on developments since the publication of the original CHARMM article in 1983.

The FoldX web server: an online force field

The core functionality of FoldX, namely the calculation of the free energy of a macromolecule based on its high-resolution 3D structure, is now publicly available through a web server at FoldX.

Using quantum mechanics to improve estimates of amino acid side chain rotamer energies

In a subset of cases these energies differ significantly from those calculated with standard molecular mechanics potentials or those derived from PDB statistics, and in these cases the energies from the QM methods result in more accurate placement of amino acid side chains in structure prediction tests.

Phage-encoded combinatorial chemical libraries based on bicyclic peptides.

A phage strategy for the selection of ligands based on bicyclic or linear peptides attached covalently to an organic core for generating and selecting bicyclic macrocycles as ligands poised at the interface of small-molecule drugs and biologics is described.
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