Modelling Solvation Thermodynamics
Inhomogeneous fluid solvation theory (IFST) is a statistical mechanical framework for calculating the effect of a solute on the free energy of the surrounding solvent relative to its bulk state. The solute can be a protein, peptide, or small molecule and the solvent is commonly water.
One of the useful features of IFST is that the free energy changes are calculated for small subvolumes surrounding the solute and this allows the contribution of different regions of space to be calculated and visualized.
This has been used to understand the determinants of binding affinity and design new inhibitors in the hit-to-lead and lead optimization stages of drug discovery. Work in this lab has focused on the importance of modeling solvation at protein surfaces, the data requirements for convergence of the thermodynamic quantities and the development of quantitatively accurate IFST software.
On the accuracy of one- and two-particle solvation entropies
Benedict W. J. Irwin and David J Huggins
Journal of Chemical Physics - 2017
A Large Scale Study of Hydration Environments Through Hydration Sites
Benedict W. J. Irwin, Sinisa Vukovic, Michael C. Payne, and David John Huggins
The Journal of Physical Chemistry B
Assimilating Radial Distribution Functions To Build Water Models with Improved Structural Properties
Alexander D. Wade, Lee-Ping Wang, and David J. Huggins
Journal of Chemical Information and Modeling
Thermodynamic Properties of Water Molecules at a Protein–Protein Interaction Surface
David J. Huggins, May Marsh, Mike C. Payne
Journal of Chemical Theory and Computation - 2011 , Volume 7: Issue 11
Computational Analysis of Phosphopeptide Binding to the Polo-box Domain of the Mitotic Kinase PLK1 Using Molecular Dynamics Simulation
David J. Huggins, Grahame J. McKenzie, Daniel D. Robinson, Ana J. Narvaez, Bryn Hardwick, Meredith Roberts-Thomson, Ashok R. Venkitaraman, Guy H. Grant and Mike C. Payne
PLoS Computational Biology - 2010, Volume 6: Issue 8
Exploring the Role of Water in Molecular Recognition: Predicting Protein Ligandability Using a Combinatorial Search of Surface Hydration Sites
Sinisa Vukovic, Paul E Brennan, David J Huggins
Journal of Physics: Condensed Matter - 2016