Cardiff University President's Research Scholarship: Drug Discovery: Interactive drug-design: using advanced computing to evaluate the induced fit effect (PhD Studentship)
Reference Number: R465
Applications will be considered on a rolling basis.
Key Studentship Information
This is a Cardiff University President's Research Scholarship, part of a new £4M investment to coincide with the inauguration of Professor Sir Martin Evans (Nobel Prize for Medicine 2007) as Cardiff’s new President. All of the University Schools and Research Centres offering opportunities under the programme have demonstrated the real potential of the Scholarships to contribute to research excellence through significant, challenging and original PhD research projects and excellent PhD supervision and support. Other attractive features of the Scholarships include the presence of multiple President’s Scholars in each of the research areas and the guaranteed exposure of President’s Scholars to innovative technologies, theories, methodological approaches, and debates. More information on the President's Research Scholarships scheme is available here: www.cardiff.ac.uk/presidents
Project Title: Interactive drug-design: using advanced computing to evaluate the induced fit effect
Project Description:
The project description is indicative at this stage and may be subject to change. Please contact Dr Andrea Brancale, brancalea@cardiff.ac.uk, for further information.
Drug discovery is a time consuming, expensive process and is often a very frustrating experience for the researchers involved. For these reasons new drug design approaches and methodologies are constantly developed in order to reduce the time and costs of this process. Recently, interest has increasingly been focused on computer-based techniques and molecular modelling, which allow the design and evaluation of novel potential drugs in silico before being prepared in a laboratory. The development of many modelling software packages is oriented toward limiting the human intervention, considered to be the bottleneck of the process. The user carries out preparation of the input and analysis of the output, leaving the rest of the discovery process to the computer.
Indeed, the use of these methodologies has led to many successes, but it would be fair to ask us if a process that relies mostly on computer pseudo-knowledge whilst, marginalizing researcher knowledge, could be really considered a rational approach. An interactive informed human intervention in a computer simulation could significantly improve the results obtained and this is particularly evident in de novo drug design applications.
Following this idea, we have developed a novel immersive molecular modelling simulator where the user uses an haptic device to probe a biological target and its interactions with a potential drug, feeling the forces and molecular interactions on his/her hand while having complete three dimensional visual feedback. The movements of the user’s hand are tracked in real time and used to steer the simulation. The project of this studentship will explore the possibility to include some degree of protein flexibility into the drug design simulations.
Currently, our software, like many de novo and molecular docking packages, treats the small molecule examined as flexible and the biological target as rigid. This is a significant approximation to the real scenario, where the target protein undergoes some conformational changes upon binding of a small molecule. The simulation of such “induced fit” would require computationally expensive calculations and we would tackle this issue by parallelising the code and by using high performance computing facilities. In particular the project will be focused on the development of the code on GP-GPUs architecture.
Supervisor: Dr. Andrea Brancale, with Dr Ian Grimstead and with Prof. Martyn Guest
Proposed Start Date: 1st October 2012
Funding
This is a Cardiff University President's Research Scholarship. The award includes full UK/EU tuition fees plus a doctoral stipend matching UK Research Council National Minimum (£13,590 p.a. for 2010/11, updated each year).
Number of Awards Available: 1
Eligibility
Academic Criteria: Applicants must have a First Class Honours degree or a 2.1 plus a postgraduate Masters degree (or their equivalents) in a relevant subject.
Applicants must also have proven software programming experience (C++; CUDA).
Residency: The scholarship is available to both UK Nationals and EU students.
How to Apply
Interested candidates should submit a CV and Covering Letter to brancalea@cardiff.ac.uk.
Applications will be considered on a rolling basis.
Further Information
For more information contact Dr Andrea Brancale:
Email: brancalea@cardiff.ac.uk
Telephone: 029 2087 4485
Web: www.cf.ac.uk/phrmy/contactsandpeople/fulltimeacademicstaff/brancale-andreanew-overview_new.html
