Markov State Models to Study the Functional Dynamics of Proteins in the Wake of Machine Learning
| Autor: | Xuhui Huang, Ilona Christy Unarta, Siqin Cao, Eshani Chrisana Goonetilleke, Kirill A. Konovalov |
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| Rok vydání: | 2021 |
| Předmět: |
non-Markovian dynamics
biomolecular function Markov chain Computer science business.industry Deep learning Dimensionality reduction Feature selection molecular dynamics simulations Machine learning computer.software_genre ENCODE Field (computer science) Chemistry conformational change machine learning Markov state models Perspective Master equation Artificial intelligence Cluster analysis business QD1-999 computer |
| Zdroj: | JACS Au JACS Au, Vol 1, Iss 9, Pp 1330-1341 (2021) |
| ISSN: | 2691-3704 |
| DOI: | 10.1021/jacsau.1c00254 |
| Popis: | Markov state models (MSMs) based on molecular dynamics (MD) simulations are routinely employed to study protein folding, however, their application to functional conformational changes of biomolecules is still limited. In the past few years, the field of computational chemistry has experienced a surge of advancements stemming from machine learning algorithms, and MSMs have not been left out. Unlike global processes, such as protein folding, the application of MSMs to functional conformational changes is challenging because they mostly consist of localized structural transitions. Therefore, it is critical to properly select a subset of structural features that can describe the slowest dynamics of these functional conformational changes. To address this challenge, we recommend several automatic feature selection methods such as Spectral-OASIS. To identify states in MSMs, the chosen features can be subject to dimensionality reduction methods such as TICA or deep learning based VAMPNets to project MD conformations onto a few collective variables for subsequent clustering. Another challenge for the application of MSMs to the study of functional conformational changes is the ability to comprehend their biophysical mechanisms, as MSMs built for these processes often require a large number of states. We recommend the recently developed quasi-MSMs (qMSMs) to address this issue. Compared to MSMs, qMSMs encode the non-Markovian dynamics via the generalized master equation and can significantly reduce the number of states. As a result, qMSMs can be built with a handful of states to facilitate the interpretation of functional conformational changes. In the wake of machine learning, we believe that the rapid advancement in the MSM methodology will lead to their wider application in studying functional conformational changes of biomolecules. |
| Databáze: | OpenAIRE |
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