A Database of Force-Field Parameters, Dynamics, and Properties of Antimicrobial Compounds

Abstract

We present an on-line database of all-atom force-field parameters and molecular properties of compounds with antimicrobial activity (mostly antibiotics and some beta-lactamase inhibitors). For each compound, we provide the General Amber Force Field parameters for the major species at physiological pH, together with an analysis of properties of interest as extracted from µs-long molecular dynamics simulations in explicit water solution. The properties include number and population of structural clusters, molecular flexibility, hydrophobic and hydrophilic molecular surfaces, the statistics of intraand inter-molecular H-bonds, as well as structural and dynamical properties of solvent molecules within first and second solvation shells. In addition, the database contains several key molecular parameters, such as energy of the frontier molecular orbitals, vibrational properties, rotational constants, atomic partial charges and electric dipole moment, computed by Density Functional Theory. The present database (to our knowledge the first extensive one including dynamical properties) is part of a wider project aiming to build-up a database containing structural, physico-chemical and dynamical properties of medicinal compounds using different force-field parameters with increasing level of complexity and reliability. The database is freely accessible at http://www.dsf.unica.it/translocation/db/.

Keywords: all-atom force fields; antimicrobial compounds; molecular databases; molecular dynamics simulations.

Figure 1

Computational protocol adopted (See Section 2 for a description).

Figure 2

Snapshots of the main page of the database (A); an individual page (B); and the General Amber Force Field parameters files downloadable for each compound (C).

Figure 3

Snapshots of the general properties available for each compound (A); the molecular net charge dependence on pH computed with MarvinSketch [30] (B); and the polar/non-polar (red-white-blue color scale) molecular surfaces evaluated with the PLATINUM server [52] (C).

Figure 4

Snapshots of the list of molecular properties exctracted from QM calculations (A); the electronic (B); and vibrational spectra (C); and the visual representation of the electric dipole moment (D).

Figure 5

Snapshots of the some of the molecular properties exctracted from MD trajectories (A); as an example we report first and second water shells and statistics of solute-solvent H-bonds (B), and the dynamical behaviour of the relative shape anisotropy (C).