Introduction

Binding sites present well-defined interaction patterns that putative ligands must meet. Knowing them is essential to guide structure-based drug discovery projects. However, complex aspects of molecular recognition-such as protein flexibility or the effect of aqueous solvation-hinder accurate predictions. This is particularly true for polar contacts, which are heavily influenced by the local environment and the behavior of discrete water molecules. Here we present and validate MDmix (Molecular Dynamics simulations with mixed solvents) as a method that provides much more accurate interaction maps than ordinary potentials (e.g., GRID). Additionally, MDmix also affords water displaceability predictions, with advantages over methods that use pure water as solvent (e.g., inhomogeneous fluid solvation theory). With current MD software and hardware solutions, predictions can be obtained in a matter of hours and visualized in a very intuitive manner. Thus, MDmix is an ideal complement in everyday structure-based drug discovery projects.

Publications

  1. Molecular simulations with solvent competition quantify water displaceability and provide accurate interaction maps of protein binding sites.
    Cite this
    Alvarez-Garcia D, Barril X, 2014-10-01 - Journal of medicinal chemistry

Credits

  1. Daniel Alvarez-Garcia
    Developer

    Departament de Fisicoquímica, Facultat de Farmàcia, Spain

  2. Xavier Barril
    Investigator

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Summary
AccessionBT000491
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByXavier Barril