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Department of Biological Sciences

Biological Sciences

This week in Department

Department of Biological Sciences Research Forum:

Details for presentation:
Date: 14.02.2026
Time: 12.00 Noon onwards
Venue: NAB Room # 6102

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Presenter: Prof. Jigneshkumar D. Prajapati
TITLE OF TALK: Molecular Simulations of Intricate Processes in Molecular Machines
ABSTRACT:
Part I: Long-Range Allostery in the RyR1 Calcium Channel
Understanding how large molecular machines coordinate long-range structural communication remains a central challenge in biophysics. Multi-million atom explicit-solvent molecular dynamics simulations were employed to dissect allosteric signal propagation in the 2.2 MDa tetrameric RyR1 calcium channel, revealing a >200 Å communication network linking peripheral regulatory domains to the pore-forming S6 helices. Stabilization of the closed state by the Rycal drug ARM210 is shown to arise from rigidification of the cytosolic shell and disruption of this allosteric pathway. Disease-relevant and oxidative stress–mimicking mutations were further demonstrated to perturb the same regulatory circuitry, providing mechanistic insight into RyR1-associated myopathies.
 
Part II: Overcoming Timescale Barriers in Ribosomal Dynamics
To address the intrinsic size and timescale limitations of atomistic simulations in megadalton assemblies, MUON, a constrained multi–rigid body simulation framework preserving atomistic detail, was developed to enable accelerated sampling of slow collective motions. Application to ribosomal tRNA dissociation captured second-scale unbinding events and resolved transition pathways and kinetic features inaccessible to conventional simulations. These results were complemented by multi-microsecond enhanced-sampling simulations, providing a thermodynamic and mechanistic description of rare-event dynamics in a massive molecular machine.
 

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All interested faculty members are invited to attend the presentation. 

All Ph.D. scholars must attend the presentations and show their active participation.