BCL::Conf: small molecule conformational sampling using a knowledge based rotamer library

Kothiwale, Sandeepkumar; Mendenhall, Jeffrey L.; Meiler, Jens

doi:10.1186/s13321-015-0095-1

Cited by 116 publications

(130 citation statements)

References 43 publications

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“…Such conformer generation is recommended subsequent to creating an initial threedimensional geometry if desired. [36,38,39,40,41,42,43,44,45]…”

Section: Resultsmentioning

confidence: 99%

Fast, Efficient Fragment-Based Coordinate Generation for Open Babel

Yoshikawa¹,

Hutchison

2019

Preprint

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Rapidly predicting an accurate three dimensional geometry of a molecule is a crucial task for cheminformatics and across a wide range of molecular modeling. Consequently, developing a fast, accurate, and open implementation of structure prediction is necessary for reproducible cheminformatics research. We introduce a fragment-based coordinate generation implementation for Open Babel, a widely-used open source toolkit for cheminformatics. The new implementation improves speed and stereochemical accuracy, while retaining or improving accuracy of bond lengths, bond angles, and dihedral torsions. Input molecules are broken into fragments by cutting at rotatable bonds. The coordinates of fragments are set according to a fragment library, prepared from open crystallographic databases. Since the coordinates of multiple atoms are decided at once, coordinate prediction is accelerated over the previous rules-based implementation in Open Babel, as well as the widely-used distance geometry methods in RDKit. This new implementation will be beneficial for a wide range of applications, including computational property prediction in polymers, molecular materials and drug design.

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“…Such conformer generation is recommended subsequent to creating an initial threedimensional geometry if desired. [36,38,39,40,41,42,43,44,45]…”

Section: Resultsmentioning

confidence: 99%

Fast, Efficient Fragment-Based Coordinate Generation for Open Babel

Yoshikawa¹,

Hutchison

2019

Preprint

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“…One hundred conformations of PGE 2 -G and thirteen conformations of UDP were generated with BCL::Conf 74 . This application builds small molecule conformations from active substructures seen in experimentally elucidated structures.…”

Section: Methodsmentioning

confidence: 99%

Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6

Brüser

Zimmermann

Crews

et al. 2017

Sci Rep

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Cyclooxygenase-2 catalyses the biosynthesis of prostaglandins from arachidonic acid but also the biosynthesis of prostaglandin glycerol esters (PG-Gs) from 2-arachidonoylglycerol. Previous studies identified PG-Gs as signalling molecules involved in inflammation. Thus, the glyceryl ester of prostaglandin E2, PGE2-G, mobilizes Ca2+ and activates protein kinase C and ERK, suggesting the involvement of a G protein-coupled receptor (GPCR). To identify the endogenous receptor for PGE2-G, we performed a subtractive screening approach where mRNA from PGE2-G response-positive and -negative cell lines was subjected to transcriptome-wide RNA sequencing analysis. We found several GPCRs that are only expressed in the PGE2-G responder cell lines. Using a set of functional readouts in heterologous and endogenous expression systems, we identified the UDP receptor P2Y6 as the specific target of PGE2-G. We show that PGE2-G and UDP are both agonists at P2Y6, but they activate the receptor with extremely different EC50 values of ~1 pM and ~50 nM, respectively. The identification of the PGE2-G/P2Y6 pair uncovers the signalling mode of PG-Gs as previously under-appreciated products of cyclooxygenase-2.

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“…We recommend the BCL [27] which is freely available from http://meilerlab.org/index.php/bclcommons for academic use but does require an additional license to the Cambridge Structural Database [28] for conformer generation. The protocol in this paper has been tested with BCL version 3.2.…”

Section: Methodsmentioning

confidence: 99%

Rosetta and the Design of Ligand Binding Sites

Moretti

Bender

Allison

et al. 2016

Methods in Molecular Biology

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Proteins that bind small molecules (ligands) can be used as biosensors, signal modulators, and sequestering agents. When naturally occurring proteins for a particular target ligand are not available, artificial proteins can be computationally designed. We present a protocol based on Rosetta Ligand to redesign an existing protein pocket to bind a target ligand. Starting with a protein structure and the structure of the ligand, Rosetta can optimize both the placement of the ligand in the pocket and the identity and conformation of the surrounding sidechains, yielding proteins that bind the target compound.

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BCL::Conf: small molecule conformational sampling using a knowledge based rotamer library

Cited by 116 publications

References 43 publications

Fast, Efficient Fragment-Based Coordinate Generation for Open Babel

Fast, Efficient Fragment-Based Coordinate Generation for Open Babel

Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6

Rosetta and the Design of Ligand Binding Sites

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