Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions
Intrinsically disordered proteins (IDPs) are highly prevalent and play important roles in biology and human diseases. It is now also recognized that many IDPs remain dynamic even in specific complexes and functional assemblies. Computer simulations are essential for deriving a molecular description...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/10/1416 |
| _version_ | 1827680074741055488 |
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| author | Xiping Gong Yumeng Zhang Jianhan Chen |
| author_facet | Xiping Gong Yumeng Zhang Jianhan Chen |
| author_sort | Xiping Gong |
| collection | DOAJ |
| description | Intrinsically disordered proteins (IDPs) are highly prevalent and play important roles in biology and human diseases. It is now also recognized that many IDPs remain dynamic even in specific complexes and functional assemblies. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for a mechanistic understanding of IDPs in biology, diseases, and therapeutics. Here, we provide an in-depth review of recent advances in the multi-scale simulation of disordered protein states, with a particular emphasis on the development and application of advanced sampling techniques for studying IDPs. These techniques are critical for adequate sampling of the manifold functionally relevant conformational spaces of IDPs. Together with dramatically improved protein force fields, these advanced simulation approaches have achieved substantial success and demonstrated significant promise towards the quantitative and predictive modeling of IDPs and their dynamic interactions. We will also discuss important challenges remaining in the atomistic simulation of larger systems and how various coarse-grained approaches may help to bridge the remaining gaps in the accessible time- and length-scales of IDP simulations. |
| first_indexed | 2024-03-10T06:42:54Z |
| format | Article |
| id | doaj.art-f337d3236e794a0484a112235a62c4ea |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T06:42:54Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f337d3236e794a0484a112235a62c4ea2023-11-22T17:33:11ZengMDPI AGBiomolecules2218-273X2021-09-011110141610.3390/biom11101416Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic InteractionsXiping Gong0Yumeng Zhang1Jianhan Chen2Department of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USAIntrinsically disordered proteins (IDPs) are highly prevalent and play important roles in biology and human diseases. It is now also recognized that many IDPs remain dynamic even in specific complexes and functional assemblies. Computer simulations are essential for deriving a molecular description of the disordered protein ensembles and dynamic interactions for a mechanistic understanding of IDPs in biology, diseases, and therapeutics. Here, we provide an in-depth review of recent advances in the multi-scale simulation of disordered protein states, with a particular emphasis on the development and application of advanced sampling techniques for studying IDPs. These techniques are critical for adequate sampling of the manifold functionally relevant conformational spaces of IDPs. Together with dramatically improved protein force fields, these advanced simulation approaches have achieved substantial success and demonstrated significant promise towards the quantitative and predictive modeling of IDPs and their dynamic interactions. We will also discuss important challenges remaining in the atomistic simulation of larger systems and how various coarse-grained approaches may help to bridge the remaining gaps in the accessible time- and length-scales of IDP simulations.https://www.mdpi.com/2218-273X/11/10/1416conformational ensembleenhanced samplinggeneralized BornGō-modelimplicit solventliquid-liquid phase transition |
| spellingShingle | Xiping Gong Yumeng Zhang Jianhan Chen Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions Biomolecules conformational ensemble enhanced sampling generalized Born Gō-model implicit solvent liquid-liquid phase transition |
| title | Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions |
| title_full | Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions |
| title_fullStr | Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions |
| title_full_unstemmed | Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions |
| title_short | Advanced Sampling Methods for Multiscale Simulation of Disordered Proteins and Dynamic Interactions |
| title_sort | advanced sampling methods for multiscale simulation of disordered proteins and dynamic interactions |
| topic | conformational ensemble enhanced sampling generalized Born Gō-model implicit solvent liquid-liquid phase transition |
| url | https://www.mdpi.com/2218-273X/11/10/1416 |
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