Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Friday Speaker Abstracts

DAMPED ELASTIC NETWORK MODEL IN THERMAL BATH ACCURATELY DESCRIBES LIPID BILAYER COLLECTIVE DYNAMICS Rajat Punia 1 ; Gaurav Goel 1 ; 1 IIT Delhi, Chemical Engineering, New Delhi, India Collective dynamics in lipid bilayers, the major constituent of biological membranes, plays important role in membrane transport, pore formation, dynamics of membrane proteins and inter- bilayer interactions including membrane fusion. Elastic network models (ENM) has shown numerous successes in describing the collective dynamics of globular and membrane proteins, polynucleotides and large protein assemblies. We show that direct application of standard ENMs to lipid-bilayer fails to describe its collective dynamics accurately and highlight the importance of system (lipid-bilayer)-environment (water) interactions, interactions across periodic boundaries and frictional effects. We present a method to construct and parameterize a lipid- bilayer ENM incorporating these important interactions. Three properties of lipid-bilayers namely (A) relative fluctuations of lipid atoms, (B) lipid bilayer undulations structure factor and (C) velocity autocorrelation of lipid atoms, all determined using molecular dynamics simulations, are used to obtain ENM parameters and friction coefficients along normal modes. The model is able to accurately describe both static and dynamic, in-plane and out-of-plane collective fluctuation properties (density and height fluctuations) of lipid bilayer at varying length scales. Material properties of DMPC lipid bilayer estimated using ENM, such as bending modulus (8.2 × 10 -20 J), lipid tilt modulus (3 × 10 -20 J nm -2 ) and thermal diffusivity (9.6 × 10 - 6 cm 2 s -1 ) are in close agreement with corresponding experimental values. Finally, we show the application of this model to predict transition pathway of two functional collective motions: (1) transient formation of water pore channels and (2) cell-penetrating peptides induced membrane pore formation. The predicted transition pathways using this model are further refined using path-metadynamics simulations to obtain transition intermediates and free energy profile along these functional transitions.

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