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.


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

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

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