QLS Seminar - Tue. 11 JUne at 2:00pm - "Modeling Cryptochromes using Generative Models" by Dionessa Biton

[Quantitative Life Sciences Section]

Dear All,

On Tuesday, 11 June at 14:00 CET, Dionessa Biton (Carl von Ossietzky 
University of Oldenburg, Germany) will give a seminar titled:

*Modeling Cryptochromes using Generative Models
*

_Abstract:_

Title: Modeling Cryptochromes using Generative Models

Migration is an observed phenomenon in birds' life which is crucial to 
the species' survival [1,2]. In several migrating avian species such as 
European blackcaps, willow warbler, or Eurasian cuckoo, migration was 
found to have a genetic basis as an inherited trait that received 
selective evolutionary pressure rather than a learned behavior [3,4]. 
Some migratory birds use the inclination of the magnetic field of the 
earth as its magnetic compass for navigation [5].  The most promising 
candidate that is responsible for the magnetoreception in avian 
navigation is the photoreceptor protein cryptochrome which is located in 
the outer segment of the photoreceptor cells [6].

Inside the cryptochrome, a radical pair [FAD^∙- TrpH^∙-] forms after a 
photon excites the FAD cofactor that is associated with the signaling of 
the protein. An electron transfer chain is then formed among tryptophans 
to create a radical pair with FAD. The rates of the individual electron 
transfer processes affect the sensitivity of the species to the magnetic 
field [7].

Previous experiments have shown that different species have varying 
magnetic field sensitivity [8]. This makes it important to rationalize 
the rates of the electron transfers for each of the different 
cryptochromes in different migratory birds.

A common approach done is to model the protein in different redox states 
of the radical pair formation using molecular dynamics and estimate 
associated the free energy [8,9]. This method however is computationally 
taxing. In this talk, we propose a method to use generative models to 
model cryptochrome using training data from molecular dynamics simulations.

We use the available data for cryptochrome from a European robin 
(ErCry4) as a training set and generate different protein conformations 
using generative adversarial networks and variational autoencoders. From 
the trained model, our goal is to generate protein conformations of 
cryptochrome of other species such as pigeon or chicken. The latent 
space distribution is modeled conditioned on the given protein structure 
of the European robin so that training can be transferred to a new 
protein structure of another species. This method can be used to quickly 
generate protein conformations such that energy and the electron 
transfer rates could be estimated for other cryptochrome structures such 
are those found in other migratory birds and in fishes.



[1]     Liedvogel, M., Åkesson, S., & Bensch, S. (2011). The genetics of 
migration on the move. Trends in ecology & evolution, 26(11), 561-569. 
https://doi.org/10.1016/j.tree.2011.07.009
[2]     Dingle, H., & Drake, V. A. (2007). What is migration?. 
Bioscience, 57(2), 113-121. https://doi.org/10.1641/B570206
[3]     Merlin, C., & Liedvogel, M. (2019). The genetics and epigenetics 
of animal migration and orientation:birds, butterflies and beyond. 
Journal of Experimental Biology, 222(Suppl_1), jeb191890. 
https://doi.org/10.1242/jeb.191890
[4]     Lundberg, M., Liedvogel, M., Larson, K., Sigeman, H., Grahn, M., 
Wright, A., ... & Bensch, S. (2017). Genetic differences between willow 
warbler migratory phenotypes are few and cluster in large haplotype 
blocks. Evolution Letters, 1(3), 155-168. https://doi.org/10.1002/evl3.15
[5]     Wiltschko, W., Munro, U., Ford, H., & Wiltschko, R. (1993). 
Magnetic inclination compass: a basis for the migratory orientation of 
birds in the Northern and Southern Hemisphere. Experientia, 49, 167-170. 
https://doi.org/10.1007/BF01989423
[6]     Ritz, T., Adem, S., & Schulten, K. (2000). A model for 
photoreceptor-based magnetoreception in birds. Biophysical journal, 
78(2), 707-718. https://doi.org/10.1016/S0006-3495(00)76629-X
[7]     Timmel, C. R., Till, U., Brocklehurst, B., Mclauchlan, K. A., & 
Hore, P. J. (1998). Effects of weak magnetic fields on free radical 
recombination reactions. Molecular Physics, 95(1), 71-89. 
https://doi.org/10.1080/00268979809483134
[8]     Xu, J., Jarocha, L. E., Zollitsch, T., Konowalczyk, M., Henbest, 
K. B., Richert, S., ... & Hore, P. J. (2021). Magnetic sensitivity of 
cryptochrome 4 from a migratory songbird. Nature, 594(7864), 535-540. 
https://doi.org/10.1038/s41586-021-03618-9
[9]     Schuhmann, F., Kattnig, D. R., & Solov’yov, I. A. (2021). 
Exploring post-activation conformational changes in pigeon cryptochrome 
4. The Journal of Physical Chemistry B, 125(34), 9652-9659. 
https://doi.org/10.1021/acs.jpcb.1c02795



_
_
_The seminar will take place in the *Common area*, Ex SISSA building, 
Second floor, via Beirut 2
_
You are all most welcome to attend!

Best regards,
Erica

-- 
Erica Sarnataro
Group Secretary
Quantitative Life Sciences
The Abdus Salam International Centre for Theoretical Physics (ICTP)
Trieste,  Italy
Tel. +39-040-2240623
www.ictp.it/research/qls.aspx
e-mail:qls at ictp.it