Markov State Model Approach to Simulate Self-Assembly

Computational modeling of assembly is challenging for many systems, because their timescales can vastly exceed those accessible to simulations. This article describes the multiMSM, which is a general framework that uses Markov state models (MSMs) to enable simulating self-assembly and self-organizat...

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Main Authors: Anthony Trubiano, Michael F. Hagan
Format: Article
Language:English
Published: American Physical Society 2024-12-01
Series:Physical Review X
Online Access:http://doi.org/10.1103/PhysRevX.14.041063
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author Anthony Trubiano
Michael F. Hagan
author_facet Anthony Trubiano
Michael F. Hagan
author_sort Anthony Trubiano
collection DOAJ
description Computational modeling of assembly is challenging for many systems, because their timescales can vastly exceed those accessible to simulations. This article describes the multiMSM, which is a general framework that uses Markov state models (MSMs) to enable simulating self-assembly and self-organization of finite-sized structures on timescales that are orders of magnitude longer than those accessible to brute-force dynamics simulations. As with traditional MSM approaches, the method efficiently overcomes free energy barriers and other dynamical bottlenecks. In contrast to previous MSM approaches to simulating assembly, the framework describes simultaneous assembly of many clusters and the consequent depletion of free subunits or other small oligomers. The algorithm accounts for changes in transition rates as concentrations of monomers and intermediates evolve over the course of the reaction. Using two model systems, we show that the multiMSM accurately predicts the concentrations of the full ensemble of intermediates on timescales required to reach equilibrium. Importantly, after constructing a multiMSM for one system concentration, yields at other concentrations can be approximately calculated without any further sampling. This capability allows for orders of magnitude additional speedup. In addition, the method enables highly efficient calculation of quantities such as free energy profiles, nucleation timescales, flux along the ensemble of assembly pathways, and entropy production rates. Identifying contributions of individual transitions to entropy production rates reveals sources of kinetic traps. The method is broadly applicable to systems with equilibrium or nonequilibrium dynamics and is trivially parallelizable and, thus, highly scalable.
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spelling doaj-art-877eef60cfd445cfa573936d343bf0952025-08-20T01:59:14ZengAmerican Physical SocietyPhysical Review X2160-33082024-12-0114404106310.1103/PhysRevX.14.041063Markov State Model Approach to Simulate Self-AssemblyAnthony TrubianoMichael F. HaganComputational modeling of assembly is challenging for many systems, because their timescales can vastly exceed those accessible to simulations. This article describes the multiMSM, which is a general framework that uses Markov state models (MSMs) to enable simulating self-assembly and self-organization of finite-sized structures on timescales that are orders of magnitude longer than those accessible to brute-force dynamics simulations. As with traditional MSM approaches, the method efficiently overcomes free energy barriers and other dynamical bottlenecks. In contrast to previous MSM approaches to simulating assembly, the framework describes simultaneous assembly of many clusters and the consequent depletion of free subunits or other small oligomers. The algorithm accounts for changes in transition rates as concentrations of monomers and intermediates evolve over the course of the reaction. Using two model systems, we show that the multiMSM accurately predicts the concentrations of the full ensemble of intermediates on timescales required to reach equilibrium. Importantly, after constructing a multiMSM for one system concentration, yields at other concentrations can be approximately calculated without any further sampling. This capability allows for orders of magnitude additional speedup. In addition, the method enables highly efficient calculation of quantities such as free energy profiles, nucleation timescales, flux along the ensemble of assembly pathways, and entropy production rates. Identifying contributions of individual transitions to entropy production rates reveals sources of kinetic traps. The method is broadly applicable to systems with equilibrium or nonequilibrium dynamics and is trivially parallelizable and, thus, highly scalable.http://doi.org/10.1103/PhysRevX.14.041063
spellingShingle Anthony Trubiano
Michael F. Hagan
Markov State Model Approach to Simulate Self-Assembly
Physical Review X
title Markov State Model Approach to Simulate Self-Assembly
title_full Markov State Model Approach to Simulate Self-Assembly
title_fullStr Markov State Model Approach to Simulate Self-Assembly
title_full_unstemmed Markov State Model Approach to Simulate Self-Assembly
title_short Markov State Model Approach to Simulate Self-Assembly
title_sort markov state model approach to simulate self assembly
url http://doi.org/10.1103/PhysRevX.14.041063
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