OFraMP: a fragment-based tool to facilitate the parametrization of large molecules

Martin Stroet; Bertrand Caron; Martin S Engler; Jimi van der Woning; Aude Kauffmann; Marc van Dijk; Mohammed El-Kebir; Koen M Visscher; Josef Holownia; Callum Macfarlane; Brian J Bennion; Svetlana Gelpi-Dominguez; Felice C Lightstone; Tijs van der Storm; Daan P Geerke; Alan E Mark; Gunnar W Klau

doi:10.1007/s10822-023-00511-7

OFraMP: a fragment-based tool to facilitate the parametrization of large molecules

J Comput Aided Mol Des. 2023 Aug;37(8):357-371. doi: 10.1007/s10822-023-00511-7. Epub 2023 Jun 13.

Authors

Martin Stroet¹, Bertrand Caron¹, Martin S Engler^{2

3}, Jimi van der Woning², Aude Kauffmann¹, Marc van Dijk⁴, Mohammed El-Kebir⁵, Koen M Visscher⁴, Josef Holownia¹, Callum Macfarlane¹, Brian J Bennion⁶, Svetlana Gelpi-Dominguez⁷, Felice C Lightstone⁶, Tijs van der Storm^{2

8}, Daan P Geerke⁴, Alan E Mark⁹, Gunnar W Klau³

Affiliations

¹ School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
² Centrum Wiskunde & Informatica, Science Park 123, 1098 XG, Amsterdam, The Netherlands.
³ Algorithmic Bioinformatics, Heinrich Heine University Düsseldorf, Universitätsstr. 1, 40225, Düsseldorf, Germany.
⁴ Department of Chemistry and Pharmaceutical Sciences, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, the Netherlands.
⁵ Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
⁶ Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, 7000 East Ave, Livermore, CA, 94552, USA.
⁷ Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT, 06269, USA.
⁸ Faculty of Science and Engineering, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
⁹ School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia. a.e.mark@uq.edu.au.

Abstract

An Online tool for Fragment-based Molecule Parametrization (OFraMP) is described. OFraMP is a web application for assigning atomic interaction parameters to large molecules by matching sub-fragments within the target molecule to equivalent sub-fragments within the Automated Topology Builder (ATB, atb.uq.edu.au) database. OFraMP identifies and compares alternative molecular fragments from the ATB database, which contains over 890,000 pre-parameterized molecules, using a novel hierarchical matching procedure. Atoms are considered within the context of an extended local environment (buffer region) with the degree of similarity between an atom in the target molecule and that in the proposed match controlled by varying the size of the buffer region. Adjacent matching atoms are combined into progressively larger matched sub-structures. The user then selects the most appropriate match. OFraMP also allows users to manually alter interaction parameters and automates the submission of missing substructures to the ATB in order to generate parameters for atoms in environments not represented in the existing database. The utility of OFraMP is illustrated using the anti-cancer agent paclitaxel and a dendrimer used in organic semiconductor devices. OFraMP applied to paclitaxel (ATB ID 35922).

Keywords: Automated topology builder; Dendrimer; Drugs; Force fields; Molecular fragments; Molecular simulation; Partial charges.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Databases, Factual
Software*