Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach

Abstract A key factor in computational drug design is the consistency and reliability with which intermolecular interactions between a wide variety of molecules can be described. Here we present a procedure to efficiently, reliably and automatically assign partial atomic charges to atoms based on kn...

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Main Authors:	Martin S. Engler, Bertrand Caron, Lourens Veen, Daan P. Geerke, Alan E. Mark, Gunnar W. Klau
Format:	Article
Language:	English
Published:	BMC 2019-02-01
Series:	Algorithms for Molecular Biology
Subjects:	Multiple-choice knapsack Integer Linear Programming Pseudo-polynomial Dynamic Programming Partial charge assignment Molecular dynamics simulations
Online Access:	http://link.springer.com/article/10.1186/s13015-019-0138-7

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spelling	doaj-f62d9c28f3f74c72a76a1a758d6078e72020-11-24T21:42:11ZengBMCAlgorithms for Molecular Biology1748-71882019-02-0114111010.1186/s13015-019-0138-7Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approachMartin S. Engler0Bertrand Caron1Lourens Veen2Daan P. Geerke3Alan E. Mark4Gunnar W. Klau5Algorithmic Bioinformatics, Heinrich Heine UniversitySchool of Chemistry & Molecular Biosciences, The University of QueenslandNetherlands eScience CenterAIMMS Division of Molecular and Computational Toxicology, Vrije UniversiteitSchool of Chemistry & Molecular Biosciences, The University of QueenslandAlgorithmic Bioinformatics, Heinrich Heine UniversityAbstract A key factor in computational drug design is the consistency and reliability with which intermolecular interactions between a wide variety of molecules can be described. Here we present a procedure to efficiently, reliably and automatically assign partial atomic charges to atoms based on known distributions. We formally introduce the molecular charge assignment problem, where the task is to select a charge from a set of candidate charges for every atom of a given query molecule. Charges are accompanied by a score that depends on their observed frequency in similar neighbourhoods (chemical environments) in a database of previously parameterised molecules. The aim is to assign the charges such that the total charge equals a known target charge within a margin of error while maximizing the sum of the charge scores. We show that the problem is a variant of the well-studied multiple-choice knapsack problem and thus weakly $$\mathcal {NP}$$ NP -complete. We propose solutions based on Integer Linear Programming and a pseudo-polynomial time Dynamic Programming algorithm. We demonstrate that the results obtained for novel molecules not included in the database are comparable to the ones obtained performing explicit charge calculations while decreasing the time to determine partial charges for a molecule from hours or even days to below a second. Our software is openly available.http://link.springer.com/article/10.1186/s13015-019-0138-7Multiple-choice knapsackInteger Linear ProgrammingPseudo-polynomial Dynamic ProgrammingPartial charge assignmentMolecular dynamics simulations
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Martin S. Engler Bertrand Caron Lourens Veen Daan P. Geerke Alan E. Mark Gunnar W. Klau
spellingShingle	Martin S. Engler Bertrand Caron Lourens Veen Daan P. Geerke Alan E. Mark Gunnar W. Klau Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach Algorithms for Molecular Biology Multiple-choice knapsack Integer Linear Programming Pseudo-polynomial Dynamic Programming Partial charge assignment Molecular dynamics simulations
author_facet	Martin S. Engler Bertrand Caron Lourens Veen Daan P. Geerke Alan E. Mark Gunnar W. Klau
author_sort	Martin S. Engler
title	Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach
title_short	Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach
title_full	Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach
title_fullStr	Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach
title_full_unstemmed	Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach
title_sort	automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach
publisher	BMC
series	Algorithms for Molecular Biology
issn	1748-7188
publishDate	2019-02-01
description	Abstract A key factor in computational drug design is the consistency and reliability with which intermolecular interactions between a wide variety of molecules can be described. Here we present a procedure to efficiently, reliably and automatically assign partial atomic charges to atoms based on known distributions. We formally introduce the molecular charge assignment problem, where the task is to select a charge from a set of candidate charges for every atom of a given query molecule. Charges are accompanied by a score that depends on their observed frequency in similar neighbourhoods (chemical environments) in a database of previously parameterised molecules. The aim is to assign the charges such that the total charge equals a known target charge within a margin of error while maximizing the sum of the charge scores. We show that the problem is a variant of the well-studied multiple-choice knapsack problem and thus weakly $$\mathcal {NP}$$ NP -complete. We propose solutions based on Integer Linear Programming and a pseudo-polynomial time Dynamic Programming algorithm. We demonstrate that the results obtained for novel molecules not included in the database are comparable to the ones obtained performing explicit charge calculations while decreasing the time to determine partial charges for a molecule from hours or even days to below a second. Our software is openly available.
topic	Multiple-choice knapsack Integer Linear Programming Pseudo-polynomial Dynamic Programming Partial charge assignment Molecular dynamics simulations
url	http://link.springer.com/article/10.1186/s13015-019-0138-7
work_keys_str_mv	AT martinsengler automatedpartialatomicchargeassignmentfordruglikemoleculesafastknapsackapproach AT bertrandcaron automatedpartialatomicchargeassignmentfordruglikemoleculesafastknapsackapproach AT lourensveen automatedpartialatomicchargeassignmentfordruglikemoleculesafastknapsackapproach AT daanpgeerke automatedpartialatomicchargeassignmentfordruglikemoleculesafastknapsackapproach AT alanemark automatedpartialatomicchargeassignmentfordruglikemoleculesafastknapsackapproach AT gunnarwklau automatedpartialatomicchargeassignmentfordruglikemoleculesafastknapsackapproach
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Automated partial atomic charge assignment for drug-like molecules: a fast knapsack approach

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