Biophysical Society Thematic Meeting| Lima 2019

Revisiting the Central Dogma of Molecular Biology at the Single-Molecule Level

Poster Abstracts

15-POS Board 15 MULTI-RESOLUTION SIMULATIONS OF INTRACELLULAR PROCESSES WITH SINGLE-MOLECULE DETAIL Radek Erban 1 ; 1 University of Oxford, Mathematical Institute, Oxford, United Kingdom Molecular dynamics (MD) approaches, based on the rules of classical mechanics, are commonly used to study the behaviour of complex biomolecules in biological applications. They are given as systems of differential equations for the time evolution of positions and velocities of particles, representing either individual atoms or groups of atoms, describing parts of a biomolecule. One of the main limitations of all-atom MD simulations is that their direct application to the modelling of intracellular behaviour is restricted to modelling processes in relatively small domains over relatively short time intervals. In particular, intracellular processes which include transport of molecules between different parts of a cell, are usually only modelled by a much coarser modelling approach, including Brownian dynamics (BD) and other stochastic reaction- diffusion models. In my presentation, I will discuss connections between MD and BD, focusing on the development, analysis and applications of multi-resolution methods for spatio-temporal modelling of intracellular processes. These methods use detailed MD simulations in localized regions of particular interest (in which accuracy and microscopic details are important) and a coarser (less-detailed) model in other regions where accuracy may be traded for simulation efficiency. Three types of multi-resolution methodologies will be considered in detail: describing the whole biomolecule (biological structure) of interest by the detailed modelling approach which is coupled with a coarse model for the solvent molecules which are far away from the biomolecule; describing different parts of a biomolecule by using models with different level of resolution;considering the region with the most detailed model as a fixed part of the physical space and allowing the biomolecule of interest to pass between this region and its surroundings, where a coarse-grained modelling approach is used.These multiscale methodologies are applied to investigate models of three intracellular processes, describing dynamics of (a) calcium, (b) actin and (c) DNA.

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