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Computation 2016, 4(1), 5; doi:10.3390/computation4010005

Extracting Conformational Ensembles of Small Molecules from Molecular Dynamics Simulations: Ampicillin as a Test Case

Dipartimento di Fisica, Università di Cagliari, Cittadella Universitaria, I-09042 Monserrato (CA), Italy
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Academic Editor: Karlheinz Schwarz
Received: 30 November 2015 / Revised: 8 January 2016 / Accepted: 21 January 2016 / Published: 26 January 2016
(This article belongs to the Section Computational Chemistry)
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Abstract

The accurate and exhaustive description of the conformational ensemble sampled by small molecules in solution, possibly at different physiological conditions, is of primary interest in many fields of medicinal chemistry and computational biology. Recently, we have built an on-line database of compounds with antimicrobial properties, where we provide all-atom force-field parameters and a set of molecular properties, including representative structures extracted from cluster analysis over μs-long molecular dynamics (MD) trajectories. In the present work, we used a medium-sized antibiotic from our sample, namely ampicillin, to assess the quality of the conformational ensemble. To this aim, we compared the conformational landscape extracted from previous unbiased MD simulations to those obtained by means of Replica Exchange MD (REMD) and those originating from three freely-available conformer generation tools widely adopted in computer-aided drug-design. In addition, for different charge/protonation states of ampicillin, we made available force-field parameters and static/dynamic properties derived from both Density Functional Theory and MD calculations. For the specific system investigated here, we found that: (i) the conformational statistics extracted from plain MD simulations is consistent with that obtained from REMD simulations; (ii) overall, our MD-based approach performs slightly better than any of the conformer generator tools if one takes into account both the diversity of the generated conformational set and the ability to reproduce experimentally-determined structures. View Full-Text
Keywords: ampicillin; molecular databases; molecular descriptors; all-atom force fields; molecular dynamics simulations; computer-aided drug design; conformer generation tools ampicillin; molecular databases; molecular descriptors; all-atom force fields; molecular dynamics simulations; computer-aided drug design; conformer generation tools
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Malloci, G.; Serra, G.; Bosin, A.; Vargiu, A.V. Extracting Conformational Ensembles of Small Molecules from Molecular Dynamics Simulations: Ampicillin as a Test Case. Computation 2016, 4, 5.

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