Mixed-gen Season 2 – Session 6 Simulating biological systems
Location: Online meeting - hosted by CECAM-HQ
This is the sixth session of the second season of the Mixed-Gen on-line series aimed mainly at PhD students and researchers in their first post-doc. Our goal is to continue providing a new venue for these young scientists to share their work, get expert feedback and have an opportunity to strengthen scientific relations within the CECAM community.
The general area for this session is Simulating biological systems
If you are a PhD student or a post-doc:
Please use the Participate Tab on this page to start the application. You will have to login using your CECAM account to access the application form. If you don't have a CECAM account yet, use the register option on the top right corner of the login page...and welcome to CECAM!
If you are a more senior scientist:
Please contact the organisers and we shall process your registration.
Submission of posters
(Please note that - at least for the time being - we shall accept posters only from PhD students or researchers in their first post-doc)
After your application is accepted, you will be able to submit a poster. In the CECAM page for this event, go to “My participation” tab and click on “Add a poster”, providing title and abstract following the recommended format. On the same form you can upload your poster file in png or jpg as soon as it is ready. These formats are strict to enable showing of the poster in the Gather session. If the poster file is not ready at the moment of submitting your abstract, you can upload it later by editing your submission (Go to “My participation” tab and click three vertical dots on “Actions” column on table “My posters”). Please upload your poster as soon as possible to enable a decision from the selection committee - see below.
Please note that posters will be visible in the Gather room associated with this session until the end of the series (June 2022) unless otherwise requested.
DEADLINE FOR SUBMISSION: TEN DAYS BEFORE THE EVENT
Selection of posters
Posters will be selected by the event organisers with the support of our main speaker and experts who will take place in the poster session.
Selection of the two talks by PhD or first year postdocs
These contributions, to be broadcasted in the Zoom webinar in the first part of the event, will be selected, after a preliminary screening by the organisers, the main speaker and guest experts, via a lottery from the posters selected for the Gather session. Please tick “No” to the question “Upgrade to talk?” in your application if you DO NOT WANT your poster to be considered for this lottery.
THE DECISION ON THE POSTER AND THE OUTCOME OF THE LOTTERY SELECTION WILL BE COMMUNICATED ONE WEEK BEFORE THE EVENT
POSTER SUBMISSIONS BEYOND THIS DEADLINE WILL BE ACCEPTED BUT NOT CONSIDERED FOR UPGRADE TO TALK. SUBMISSION WILL BE DEFINITELY CLOSED FOUR DAYS BEFORE THE EVENT.
SESSION 6. Title and abstract of talks
Using Computer Simulations to Advance our Understanding of Biological Systems at the Atomic Level
Benoit Roux, The University of Chicago
Classical molecular dynamics simulations based on atomic models play an increasingly important role in a wide range of applications in physics, biology and chemistry. The approach consists of constructing detailed atomic models of the macromolecular system and, having described the microscopic forces with a potential function, using Newton's classical equation, F=MA, to literally "simulate" the dynamical motions of all the atoms as a function of time. The calculated trajectory, though an approximation to the real world, provides detailed information about the time course of the atomic motions, which is impossible to access experimentally. Specialized free energy simulations are also an important route to establish a strong connection to experiments. The development of efficient methods for simulating slow conformational transitions is another subject of great interest in computational studies of biomolecular system. A powerful paradigm for mapping the conformational landscape of biomolecular systems is to combine free energy methods, transition pathway techniques and stochastic Markov State Model based massively distributed simulations. These concepts will be illustrated with a few recent computational studies of Src tyrosine kinases, K+ channels, and the P-type ion pumps.
Asparagine tautomerization in glycosyltransferase catalysis. The molecular mechanism of protein O-fucosyltransferase 1
Beatriz Piniello Castillo, University of Barcelona
Enzyme O-fucosyltransferase 1 (POFUT1) catalyzes the transfer of one moiety of L-fucose to a threonine or serine residue in the surface of epidermic growth factor-like domains (EGF-LD), small peptides involved in the Notch signaling cascade. Unlike most inverting glycosyltransferases, POFUT1 lacks a basic residue in the active site that could act as a catalytic base to deprotonate the Thr/Ser residue of the EGF-LD acceptor during the chemical reaction. Using quantum mechanics/molecular mechanics (QM/MM) metadynamics methods , we have uncovered the enzyme’s catalytic mechanism, which involves proton shuttling through a conserved active site asparagine that undergoes tautomerization . Experimental kinetic analysis of Caenorhabditis elegans POFUT1 Asn43 mutants support this result, as the enzymatic activity was ablated even when mutated to aspartate. These findings will aid inhibitor development for Notch-associated O-glycosylation disorders.
 B. Holdener, R. Haltiwanger, Current Opinion in Structural Biology, 56, 78-86 (2019)
 A. Laio, J. VandeVondele, U. Rothlisberger, The Journal of Chemical Physics, 116, 6941-6947 (2002)
 A. Laio, M. Parrinello, Proc. Natl. Acad. Sci. U.S.A., 99, 12562-12566 (2002)
 B. Piniello, E. Lira-Navarrete, H. Takeuchi, M. Takeuchi, R. Haltiwanger, R. Hurtado-Guerrero, C. Rovira, ACS Catal., 11, 9926-9932 (2021)
Entropy of water in protein condensates
Saumyak Mukherjee, Ruhr University Bochum
Liquid liquid phase separation (LLPS) of proteins is a spontaneous and reversible process that generates membraneless oraganelle-like protein condensates. Although extensive research has been dedicated to understand this process, the underlying thermodynamic contributions remain elusive. In this project, we study the entropy of water in such protein condesates to understand its contribution towards condensate formation. For our studies, we use all atom molecular dynamics simulations on two proteins, namely human gammaD-crystallin (globular protein) and the low complexity domain of fused in sarcoma RNA binding protein (FUS-LCD) (intrinsically disordered prpotein (IDP)).
Sara Bonella (CECAM HQ) - Organiser
Ignacio Pagonabarraga (CECAM HQ) - Organiser