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Conformational space of clindamycin studied by ab initio and full-atom molecular dynamics

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Abstract

Molecular dynamics (MD) simulations allow determining internal flexibility of molecules at atomic level. Using ab initio Born–Oppenheimer molecular dynamics (BOMD), one can simulate in a reasonable time frame small systems with hundreds of atoms, usually in vacuum. With quantum mechanics/molecular mechanics (QM/MM) or full-atom molecular dynamics (FAMD), the influence of the environment can also be simulated. Here, we compare three types of MD calculations: ab initio BOMD, hybrid QM/MM, and classical FAMD. As a model system, we use a small antibiotic molecule, clindamycin, which is one of the lincosamide antibiotics. Clindamycin acquires two energetically stable forms and we investigated the transition between these two experimentally known conformers. We performed 60-ps BOMD simulations in vacuum, 50-ps QM/MM, and 100-ns FAMD in explicit water. The transition between two antibiotic conformers was observed using both BOMD and FAMD methods but was not noted in the QM/MM simulations.

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Acknowledgments

Computational resources were provided by the Interdisciplinary Centre for Mathematical and Computational Modelling of the University of Warsaw by grants G31-4 G31-13 and G59-9. The authors acknowledge support from the University of Warsaw (CeNT/BST), National Science Centre (DEC-2012/05/B/NZ1/00035 and UMO-2013/09/N/ST4/00932).

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Authors and Affiliations

  1. Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawińskiego 5A, 02-106, Warsaw, Poland

    Katarzyna Kulczycka-Mierzejewska

  2. College of Inter-faculty Individual Studies in Mathematics and Natural Science, University of Warsaw, Żwirki i Wigury 93, 02-089, Warsaw, Poland

    Katarzyna Kulczycka-Mierzejewska

  3. Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland

    Joanna Trylska

  4. Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warsaw, Poland

    Joanna Sadlej

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  1. Katarzyna Kulczycka-Mierzejewska
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Correspondence to Joanna Sadlej.

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Kulczycka-Mierzejewska, K., Trylska, J. & Sadlej, J. Conformational space of clindamycin studied by ab initio and full-atom molecular dynamics. J Mol Model 22, 20 (2016). https://doi.org/10.1007/s00894-015-2881-0

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