For a number of years I have been working on methods for validating computational models of structures [see ‘Model validation‘ on September 18th 2012] using the full potential of measurements made with modern techniques such as digital image correlation [see ‘256 shades of grey‘ on January 22nd 2014] and thermoelastic stress analysis [see ‘Counting photons to measure stress‘ on November 18th 2015]. Usually the focus of our interest is at the macroscale, for example the research on aircraft structures in the MOTIVATE project; however, in a new PhD project with colleagues at the National Tsing Hua University in Taiwan, we are planning to explore using our validation procedures and metrics  in structural biology.
The size and timescale of protein-structure thermal fluctuations are essential to the regulation of cellular functions. Measurement techniques such as x-ray crystallography and transmission electron cryomicroscopy (Cryo-EM) provide data on electron density distribution from which protein structures can be deduced using molecular dynamics models. Our aim is to develop our validation metrics to help identify, with a defined level of confidence, the most appropriate structural ensemble for a given set of electron densities. To make the problem more interesting and challenging the structure observed by x-ray crystallography is an average or equilibrium state because a folded protein is constantly in motion undergoing harmonic oscillations, each with different frequencies and amplitude .
The PhD project is part of the dual PhD programme of the University of Liverpool and National Tsing Hua University. Funding is available in form of a fee waiver and contribution to living expenses for four years of study involving significant periods (perferably two years) at each university. For more information follow this link.
 Dvurecenska, K., Graham, S., Patelli, E. & Patterson, E.A., A probabilistic metric for the validation of computational models, Royal Society Open Society, 5:180687, 2018.
 Justin Chan, Hong-Rui Lin, Kazuhiro Takemura, Kai-Chun Chang, Yuan-Yu Chang, Yasumasa Joti, Akio Kitao, Lee-Wei Yang. An efficient timer and sizer of protein motions reveals the time-scales of functional dynamics in the ribosome (2018) https://www.biorxiv.org/content/early/2018/08/03/384511.
Image: A diffraction pattern and protein structure from http://xray.bmc.uu.se/xtal/
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