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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Accounting for Electrostatic Polarization in Gas-Phase Simulations of Ion Mobility Spectrometry

Molecular dynamics (MD) simulations coupled with ion mobility spectrometry (IMS), a gas-phase extension to mass spectrometry that further filters the analytes by their topology, allows researchers to perform three dimensional structural elucidation of nucleic acids. Recently combined IMS-MD studies of short DNA duplexes (Porrini et al, 2017) and hairpins (Lippens et al, 2016), however, have struggled with obtaining accurately compact structures that agree with the experimentally determined collision cross sections for parts of their work. Because IMS experiments are performed on charged molecules, long range electrostatic interactions, as well as the changes in charge density due to protonated phosphate sites along the backbone, play a crucial role in understanding how nucleic acids behave in a gaseous environment and can benefit from a detailed quantum chemical analysis.

In the work presented here, we explore what a properly tuned electrostatic force field for nucleic acids might look like. Based off of density functional theory calculations of small oligonucleotides, we examine how one could adjust the partial charges in an MD force field to more accurately replicate Coulomb interactions for charged and protonated nucleic acids. Since the electrostatic interactions used in most force fields are often based off of single monomer quantum chemistry data and do not account for hydrogen bonding energies, the work presented here proposes new methods for parameterizing force fields using multiple oligonucleotide geometries and, more generally, how polarization is accounted for throughout an MD simulation.

Alan A. Chen is supported by NSF award #MCB1651877 .

References

    Porrini, M., Rosu, F., Rabin, C., Darré, L., Gómez, H., Orozco, M., & Gabelica, V. (2017). Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry. ACS Central Science 2017 3 (5). 454-461.

    Lippens, J. L., Ranganathan, S. V., D'Esposito, R. J., & Fabris, D. (2016). Modular calibrant sets for the structural analysis of nucleic acids by ion mobility spectrometry mass spectrometry. Analyst 141, 4084–4099.

    Rueda, M., Kalko, S. G., Luque, F. J., & Orozco, M. (2003). The Structure and Dynamics of DNA in the Gas Phase. Journal of the American Chemical Society125 (26), 8007-8014.

Christopher A. Myers1
Alan A. Chen 2, 3

1 Physics Department
2Chemistry Department
3 RNA Institute
University at Albany (SUNY)
Albany, NY 12222

Email: achen6@albany.edu