Tag Archives: modeling

Same problems in a different language

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I spent a lot of time on trains last week.  I left Liverpool on Tuesday evening for Bristol and spent Wednesday at Airbus in Filton discussing the implementation of the technologies being developed in the EU Clean Sky 2 projects MOTIVATE and DIMES.  On Wednesday evening I travelled to Bracknell and on Thursday gave a seminar at Syngenta on model credibility in predictive toxicology before heading home to Liverpool.  But, on Friday I was on the train again, to Manchester this time, to listen to a group of my PhD students presenting their projects to their peers in our new Centre for Doctoral Training called Growing skills for Reliable Economic Energy from Nuclear, or GREEN.  The common thread, besides the train journeys, is the Fidelity And Credibility of Testing and Simulation (FACTS).  My research group is working on how we demonstrate the fidelity of predictions from models, how we establish trust in both predictions from computational models and measurements from experiments that are often also ‘models’ of the real world.  The issues are similar whether we are considering the structural performance of aircraft [as on Wednesday], the impact of agro-chemicals [as on Thursday], or the performance of fusion energy and the impact of a geological disposal site [as on Friday] (see ‘Hierarchical modelling in engineering and biology‘ on March 14th, 2018) .  The scientific and technical communities associated with each application talk a different language, in the sense that they use different technical jargon and acronyms; and they are surprised and interested to discover that similar problems are being tackled by communities that they rarely think about or encounter.

Spatial-temporal models of protein structures

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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 [1] 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 [2].

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.

References:

[1] 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.

[2] 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/

Models as fables

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moel arthurIn his book, ‘Economic Rules – Why economics works, when it fails and how to tell the difference‘, Dani Rodrik describes models as fables – short stories that revolve around a few principal characters who live in an unnamed generic place and whose behaviour and interaction produce an outcome that serves as a lesson of sorts.  This seems to me to be a healthy perspective compared to the almost slavish belief in computational models that is common today in many quarters.  However, in engineering and increasingly in precision medicine, we use computational models as reliable and detailed predictors of the performance of specific systems.  Quantifying this reliability in a way that is useful to non-expert decision-makers is a current area of my research.  This work originated in aerospace engineering where it is possible, though expensive, to acquire comprehensive and information-rich data from experiments and then to validate models by comparing their predictions to measurements.  We have progressed to nuclear power engineering in which the extreme conditions and time-scales lead to sparse or incomplete data that make it more challenging to assess the reliability of computational models.  Now, we are just starting to consider models in computational biology where the inherent variability of biological data and our inability to control the real world present even bigger challenges to establishing model reliability.

Sources:

Dani Rodrik, Economic Rules: Why economics works, when it fails and how to tell the difference, Oxford University Press, 2015

Patterson, E.A., Taylor, R.J. & Bankhead, M., A framework for an integrated nuclear digital environment, Progress in Nuclear Energy, 87:97-103, 2016

Hack, E., Lampeas, G. & Patterson, E.A., An evaluation of a protocol for the validation of computational solid mechanics models, J. Strain Analysis, 51(1):5-13, 2016.

Patterson, E.A., Challenges in experimental strain analysis: interfaces and temperature extremes, J. Strain Analysis, 50(5): 282-3, 2015

Patterson, E.A., On the credibility of engineering models and meta-models, J. Strain Analysis, 50(4):218-220, 2015