Biology subjects

Ippoliti, E.

Publications and source records attributed to Ippoliti, E..

3 recordsLinked to original sources

bioRxiv2025

IR spectroscopy: from experimental spectra to high-resolution structural analysis by integrating simulations and machine learning

Understanding biomolecular function at the atomic scale requires detailed insight into the structural changes underlying dynamic processes. Vibrational infrared (IR) spectroscopy--when paired with biomolecular simulations and quantum-chemical calculations--determines bond length variations on the order of 0.01 [A], providing insights into these structutral changes. Here, we address the forward problem in IR spectroscopy: predicting high-accuracy vibrational spectra from known molecular structures identified by biomolecular simulations. Solving this problem lays the groundwork for the inverse problem: inferring structural ensembles directly from experimental IR spectra. We evaluate two computational approaches, normal mode analysis and Fourier-transformed dipole autocorrelation, against experimental IR spectra of N-Methylacetamide, a prototypical model for peptide bond vibrations. Spectra are derived from simulation models at multiple levels of theory, including hybrid quantum mechanics/molecular mechanics, machine-learned and classical molecular mechanics approaches. Our results highlight the capabilities and limitations of current theoretical biophysical approaches to decode structural information from experimental vibrational spectroscopy data. These insights underscore the potential of future artificial intelligence (AI)-enhanced models to enable direct IR-based structure determination. For example, resolving the so far experimentally inaccessible structures of toxic oligomers involved in neurodegenerative diseases, enabling improved disease diagnostics and targeted therapies. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/665767v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@6603d3org.highwire.dtl.DTLVardef@1852c85org.highwire.dtl.DTLVardef@2ddaccorg.highwire.dtl.DTLVardef@77b554_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2023

Physical Chemistry of Drug Permeation through the Cell Membrane with Atomistic Detail

We provide a molecular-level description of the thermodynamics and mechanistic aspects of drug permeation through the cell membrane. As a case study, we considered the anti-malaria, FDA approved drug chloroquine. Molecular dynamics simulations of the molecule (in its neutral and protonated form) were performed in the presence of different lipid bilayers, with the aim of uncovering key aspects of the permeation process, a fundamental step for drugs action. Free energy values obtained by well-tempered metadynamics simulations suggest that the neutral form is the only permeating protomer, consistent with experimental data. H-bond interactions of the drug with water molecules and membrane headgroups play a crucial role for permeation. The presence of the transmembrane potential, investigated here for the first time in a drug permeation study, does not qualitatively affect these conclusions. TOC Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/550356v1_ufig1.gif" ALT="Figure 1"> View larger version (71K): org.highwire.dtl.DTLVardef@d1f5b9org.highwire.dtl.DTLVardef@5b6b0forg.highwire.dtl.DTLVardef@1d1b55borg.highwire.dtl.DTLVardef@d96b52_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Proton Transfers to DNA in Native Electrospray Ionization Mass Spectrometry: A QM/MM Study.

Native electrospray ionization - ion mobility mass spectrometry (N-ESI/IM-MS) is a powerful approach for low-resolution structural studies of DNAs in the free state and in complex with ligands. Solvent vaporization is coupled with proton transfers from ammonium ions to the DNA resulting in a reduction of the DNA charge. Here we provide insight on these processes by classical MD and QM/MM free energy calculations on the (GpCpGpApApGpC) heptamer, for which a wealth of experiments is available. Our multiscale simulations, consistent with experimental data, reveal a highly complex scenario: the proton either sits on one of the molecules or is fully delocalized on both, depending on the level of hydration of the analytes and on size of the droplets formed during the electrospray experiments. This work complements our previous study on the intramolecular proton transfer on the same heptamer occurring after the processes studied here, and, together, provide a first molecular view of proton transfer in N-ESI/IM-MS. TOC GRAPHICS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/511116v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@3d85d3org.highwire.dtl.DTLVardef@11ce1d1org.highwire.dtl.DTLVardef@12d932corg.highwire.dtl.DTLVardef@1196de8_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗