Postgrad LIVE! Study Fairs

Southampton | Bristol

Nottingham Trent University Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes
FindA University Ltd Featured PhD Programmes
University of Portsmouth Featured PhD Programmes
Birkbeck, University of London Featured PhD Programmes

PhD Studentship – Free energy calculations in drug discovery

Project Description

Protein-ligand binding free energy is a crucial property used in the discovery and optimisation of novel drugs. In the context of computer-aided drug design, being able to calculate accurate, precise and reproducible binding free energies in silico is essential in terms of reducing the amount of trial-and-error synthetic effort required to develop a candidate drug. More potent and selective compounds will bind strongly to the desired target, and show weak binding to related proteins. Recent commercial software products have pushed the use of binding free energy calculations into mainstream development pipelines within the pharmaceutical industry. Even with pre-screening of suitable target systems, however, the required predictive accuracy of 1 kcal mol-1 is only attained in around half of cases. Determining whether sufficient accuracy has been achieved for a particular system is currently not possible a priori and requires expensive and time-consuming experimental validation.

In this project the accuracy of these free energy calculations in the context of the pharmaceutical industry will be explored. We will develop a large dataset of test systems based on published data and determine the sensitivity of the calculated free energies to the choice of simulation software, parameters, free energy calculation method and system setup. Based on this sensitivity analysis, the project objectives are twofold:
1. To identify the primary causes of inaccuracy in protein-ligand binding free energy calculations. Through this we will be able to identify a priori on which systems these approaches will be successful. This information will be extremely valuable, allowing those cases where the methods will be useful to be identified without requiring extensive and expensive experimental validation.
2. To improve free energy calculation methodology to address these sensitivities. We have considerable experience of optimising free energy methodology, including in recent years the use of advanced force fields and enhanced sampling methods.

Funding Notes

The project is funded for 3 ½ years and welcomes applicants from the UK and EU who have or expect to obtain at least an upper second class degree in Chemistry, Physics, Biochemistry or allied subjects/relevant disciplines. Funding will cover fees and a stipend at current research council rates of £ 14,777per annum.

Due to funding restrictions this position is only open to UK students and EU students who meet the RCUK eligibility criteria


Applications for a PhD in Chemistry should be submitted online at

Please ensure you select the academic session 2018-2019 in the academic year field and click on the Research radio button. Enter Chemistry in the search text field.

Please place ESSEX in the field for proposed supervisor/project

General enquiries should be made to Prof Jon Essex at [email protected] Any queries on the application process should be made to [email protected]

Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified

How good is research at University of Southampton in Chemistry?

FTE Category A staff submitted: 44.80

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here
* required field
Send a copy to me for my own records.

Your enquiry has been emailed successfully

FindAPhD. Copyright 2005-2019
All rights reserved.