Rescuing off-equilibrium simulation data through dynamic experimental data with dynAMMo

Christopher Kolloff

doi:10.1088/2632-2153/ad10ce

2023-12-12

Christopher Kolloff

Simon Olsson *

DOI：10.1088/2632-2153/ad10ce

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摘要

En 中文

Long-timescale behavior of proteins is fundamental to many biological processes. Molecular dynamics (MD) simulations and biophysical experiments are often used to study protein dynamics. However, high computational demands of MD limit what timescales are feasible to study, often missing rare events, which are critical to explain experiments. On the other hand, experiments are limited by low resolution. We present dynamic augmented Markov models (dynAMMo) to bridge the gap between these data and overcome their respective limitations. For the first time, dynAMMo enables the construction of mechanistic models of slow exchange processes that have been not observed in MD data by integrating dynamic experimental observables. As a consequence, dynAMMo allows us to bypass costly and extensive simulations, yet providing mechanistic insights of the system. Validated with controlled model systems and a well-studied protein, dynAMMo offers a new approach to quantitatively model protein dynamics on long timescales in an unprecedented manner.

Keyword:

Markov state models

dynamic Augmented Markov models

protein dynamics

molecular dynamics simulations

relaxation dispersion spectroscopy

chemical exchange

期刊

Machine Learning-Science and Technology

IF:

4.6

论文数:

1.1K

被引数:

3.4K

机构

chalmers university of technology

学者数:

1.5W

论文数: 1.6W

被引数: 10

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