A Force Field with Discrete Displaceable Waters and Desolvation Entropy for Hydrated Ligand Docking

Citations Over TimeTop 10% of 2011 papers

Abstract

In modeling ligand-protein interactions, the representation and role of water are of great importance. We introduce a force field and hydration docking method that enables the automated prediction of waters mediating the binding of ligands with target proteins. The method presumes no prior knowledge of the apo or holo protein hydration state and is potentially useful in the process of structure-based drug discovery. The hydration force field accounts for the entropic and enthalpic contributions of discrete waters to ligand binding, improving energy estimation accuracy and docking performance. The force field has been calibrated and validated on a total of 417 complexes (197 training set; 220 test set), then tested in cross-docking experiments, for a total of 1649 ligand-protein complexes evaluated. The method is computationally efficient and was used to model up to 35 waters during docking. The method was implemented and tested using unaltered AutoDock4 with new force field tables.

Related Papers

• → Ligand−Protein Docking with Water Molecules(2008)150 cited
• → Towards Ligand Docking Including Explicit Interface Water Molecules(2013)78 cited
• → A Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding(2020)15 cited
• → A Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding(2020)1 cited
• → A Reliable and Accurate Solution to the Induced Fit Docking Problem for Protein-Ligand Binding(2020)1 cited