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 intra- and 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/.
Highlights
The study of dynamical interactions between drugs and their biological targets is of paramount importance in medicinal chemistry and related fields.Among the many tools, numerical computations including molecular dynamics (MD) simulations have gained an ever increasing role in addressing key structural, dynamical, thermodynamic and kinetic features at a molecular level of detail [3,4,5,6,7,8,9,10,11]
Dynamical interactions can be described in MD simulations by means of different models: from full-quantum descriptions further approximations lead to mixed classical-quantum (QM/MM), all-atom, mixed molecular mechanics/coarse-grained (MM/CG) and coarse-grained (CG)
MD simulations based on all-atom empirical “force-fields”, nowadays routinely performed in the microsecond timescale, have been proven to yield structural, dynamical, thermodynamical, and kinetic information with good accuracy [5,14,15]
Summary
The study of dynamical interactions between drugs and their biological targets (such as nucleic acids and proteins) is of paramount importance in medicinal chemistry and related fields (see e.g., [1,2]).Among the many tools, numerical computations including molecular dynamics (MD) simulations have gained an ever increasing role in addressing key structural, dynamical, thermodynamic and kinetic features at a molecular level of detail [3,4,5,6,7,8,9,10,11]. MD simulations based on all-atom empirical “force-fields”, nowadays routinely performed in the microsecond timescale, have been proven to yield structural, dynamical, thermodynamical, and kinetic information with good accuracy [5,14,15]. Irrespective of the physical model used to describe interatomic forces, the key ingredient of empirical MD simulations are the parameters entering terms of the force-field, which are usually fitted to reference experimental or theoretical data [18]. The use of the latter scheme, facilitated by the introduction of the Amber
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