Multiscale simulation of actin filaments and actin-associated proteins
- 470 Downloads
Actin is an important cytoskeletal protein that serves as a building block to form filament networks that span across the cell. These networks are orchestrated by a myriad of other cytoskeletal entities including the unbranched filament–forming protein formin and branched network–forming protein complex Arp2/3. Computational models have been able to provide insights into many important structural transitions that are involved in forming these networks, and into the nature of interactions essential for actin filament formation and for regulating the behavior of actin-associated proteins. In this review, we summarize a subset of such models that focus on the atomistic features and those that can integrate atomistic features into a larger picture in a multiscale fashion.
KeywordsCoarse-graining Cytoskeleton Protein dynamics Protein-protein interactions Molecular dynamics Enhanced sampling
Compliance with ethical standards
This study was financially supported in part by the National Science Foundation through NSF Grant CHE-1465248 and Materials Research Science and Engineering Center (MRSEC) grant DMR-14207090, and Department of Defense Army Research Office (ARO) through MURI grant W911NF1410403.
Conflict of interest
Fikret Aydin declares that he has no conflict of interest. Harshwardhan H. Katkar declares that he has no conflict of interest. Gregory A. Voth declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- Aydin F, Courtemanche N, Pollard TD, Voth GA (2018) Gating mechanisms during actin filament elongation by formins Elife 7 https://doi.org/10.7554/eLife.37342
- Bidone TC, Kim T, Deriu MA, Morbiducci U, Kamm RD (2015) Multiscale impact of nucleotides and cations on the conformational equilibrium, elasticity and rheology of actin filaments and crosslinked networks. Biomech Model Mechanobiol 14:1143–1155. https://doi.org/10.1007/s10237-015-0660-6 CrossRefGoogle Scholar
- Caby M, Hardas P, Ramachandran S, Ryckaert JP (2012) Hybrid molecular dynamics simulations of living filaments. J Chem Phys 136 https://doi.org/10.1063/1.3694672
- Carlier M, Pantaloni D, Korn E (1987) The mechanisms of Atp hydrolysis accompanying the polymerization of mg-actin and Ca-actin. J Biol Chem 262:3052–3059Google Scholar
- Chou SZ, Pollard TD (2018) Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides. bioRxiv https://doi.org/10.1101/309534 (preprint posted April 27, 2018)
- Espinoza-Sanchez S, Metskas LA, Chou SZ, Rhoades E, Pollard TD (2018) Conformational changes in Arp2/3 complex induced by ATP, WASp-VCA, and actin filaments. Proc Natl Acad Sci U S A https://doi.org/10.1073/pnas.1717594115
- Guo KK, Xiao WJ, Qiu D (2011) Polymerization of actin filaments coupled with adenosine triphosphate hydrolysis: Brownian dynamics and theoretical analysis. J Chem Phys 135 https://doi.org/10.1063/1.3634006
- Katkar HH, Davtyan A, Durumeric AEP, Hocky GM, Schramm AC, De La Cruz EM, Voth GA (2018) Insights into the cooperative nature of ATP hydrolysis in actin filaments. Biophys J in press https://doi.org/10.1016/j.bpj.2018.08.034
- Popov K, Komianos J, Papoian GA (2016) MEDYAN: mechanochemical simulations of contraction and polarity alignment in actomyosin networks. PLoS Comput Biol 12 https://doi.org/10.1371/journal.pcbi.1004877
- Saunders MG, Voth GA (2013) Coarse-graining methods for computational biology. Annu Rev Biophys 42:73–93. https://doi.org/10.1146/annurev-biophys-083012-130348 CrossRefGoogle Scholar
- Sun R, Sode O, Dama JF, Voth GA (2017) Simulating protein mediated hydrolysis of ATP and other nucleoside triphosphates by combining QM/MM molecular dynamics with advances in metadynamics. J Chem Theory Comput 13:2332–2341. https://doi.org/10.1021/acs.jctc.7b00077 CrossRefPubMedCentralPubMedGoogle Scholar
- Wertman KF, Drubin DG, Botstein D (1992) Systematic mutational analysis of the yeast. ACT1 gene Genetics 132:337–350Google Scholar