Advances in Coarse-grained Modeling of Macromolecular Complexes

Overview

Journal Curr Opin Struct Biol

Date 2018 Dec 4

PMID 30508766

Citations 49

Authors

Alexander J Pak

Gregory A Voth

Affiliations

Soon will be listed here.

Abstract

Recent progress in coarse-grained (CG) molecular modeling and simulation has facilitated an influx of computational studies on biological macromolecules and their complexes. Given the large separation of length-scales and time-scales that dictate macromolecular biophysics, CG modeling and simulation are well-suited to bridge the microscopic and mesoscopic or macroscopic details observed from all-atom molecular simulations and experiments, respectively. In this review, we first summarize recent innovations in the development of CG models, which broadly include structure-based, knowledge-based, and dynamics-based approaches. We then discuss recent applications of different classes of CG models to explore various macromolecular complexes. Finally, we conclude with an outlook for the future in this ever-growing field of biomolecular modeling.

Citing Articles

Understanding the coarse-grained free energy landscape of phospholipids and their phase separation.

Sahrmann P, Voth G Biophys J. 2025; 124(4):620-636.

PMID: 39982441 PMC: 11900191. DOI: 10.1016/j.bpj.2024.12.030.

COCOMO2: A Coarse-Grained Model for Interacting Folded and Disordered Proteins.

Jussupow A, Bartley D, Lapidus L, Feig M J Chem Theory Comput. 2025; 21(4):2095-2107.

PMID: 39908323 PMC: 11866933. DOI: 10.1021/acs.jctc.4c01460.

Molecular dynamics and machine learning stratify motion-dependent activity profiles of S-layer destabilizing nanobodies.

Cecil A, Sogues A, Gurumurthi M, Lane K, Remaut H, Pak A PNAS Nexus. 2024; 3(12):pgae538.

PMID: 39660065 PMC: 11631148. DOI: 10.1093/pnasnexus/pgae538.

COCOMO2: A coarse-grained model for interacting folded and disordered proteins.

Jussupow A, Bartley D, Lapidus L, Feig M bioRxiv. 2024; .

PMID: 39554101 PMC: 11565878. DOI: 10.1101/2024.10.29.620916.

Enhancing the Assembly Properties of Bottom-Up Coarse-Grained Phospholipids.

Sahrmann P, Voth G J Chem Theory Comput. 2024; 20(22):10235-10246.

PMID: 39535391 PMC: 11604101. DOI: 10.1021/acs.jctc.4c00905.

References

Theisen K, Desai N, Volski A, Dima R . Mechanics of severing for large microtubule complexes revealed by coarse-grained simulations. J Chem Phys. 2013; 139(12):121926. DOI: 10.1063/1.4819817. View

Hyeon C, Lorimer G, Thirumalai D . Dynamics of allosteric transitions in GroEL. Proc Natl Acad Sci U S A. 2006; 103(50):18939-44. PMC: 1748156. DOI: 10.1073/pnas.0608759103. View

Hyeon C, Dima R, Thirumalai D . Pathways and kinetic barriers in mechanical unfolding and refolding of RNA and proteins. Structure. 2006; 14(11):1633-45. DOI: 10.1016/j.str.2006.09.002. View

Marsh J, Teichmann S . Structure, dynamics, assembly, and evolution of protein complexes. Annu Rev Biochem. 2014; 84:551-75. DOI: 10.1146/annurev-biochem-060614-034142. View

Sanyal T, Shell M . Coarse-grained models using local-density potentials optimized with the relative entropy: Application to implicit solvation. J Chem Phys. 2016; 145(3):034109. DOI: 10.1063/1.4958629. View

Go N . Theoretical studies of protein folding. Annu Rev Biophys Bioeng. 1983; 12:183-210. DOI: 10.1146/annurev.bb.12.060183.001151. View

Kaynak B, Findik D, Doruker P . RESPEC Incorporates Residue Specificity and the Ligand Effect into the Elastic Network Model. J Phys Chem B. 2017; 122(21):5347-5355. DOI: 10.1021/acs.jpcb.7b10325. View

Koehl P, Poitevin F, Navaza R, Delarue M . The Renormalization Group and Its Applications to Generating Coarse-Grained Models of Large Biological Molecular Systems. J Chem Theory Comput. 2017; 13(3):1424-1438. DOI: 10.1021/acs.jctc.6b01136. View

Shashkova S, Leake M . Single-molecule fluorescence microscopy review: shedding new light on old problems. Biosci Rep. 2017; 37(4). PMC: 5520217. DOI: 10.1042/BSR20170031. View

10.

Pak A, Grime J, Sengupta P, Chen A, Durumeric A, Srivastava A . Immature HIV-1 lattice assembly dynamics are regulated by scaffolding from nucleic acid and the plasma membrane. Proc Natl Acad Sci U S A. 2017; 114(47):E10056-E10065. PMC: 5703280. DOI: 10.1073/pnas.1706600114. View

11.

Henderson R . Overview and future of single particle electron cryomicroscopy. Arch Biochem Biophys. 2015; 581:19-24. DOI: 10.1016/j.abb.2015.02.036. View

12.

Atilgan A, Durell S, Jernigan R, Demirel M, Keskin O, Bahar I . Anisotropy of fluctuation dynamics of proteins with an elastic network model. Biophys J. 2001; 80(1):505-15. PMC: 1301252. DOI: 10.1016/S0006-3495(01)76033-X. View

13.

Izvekov S, Voth G . A multiscale coarse-graining method for biomolecular systems. J Phys Chem B. 2006; 109(7):2469-73. DOI: 10.1021/jp044629q. View

14.

Miyazawa S, Jernigan R . Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading. J Mol Biol. 1996; 256(3):623-44. DOI: 10.1006/jmbi.1996.0114. View

15.

Noid W, Liu P, Wang Y, Chu J, Ayton G, Izvekov S . The multiscale coarse-graining method. II. Numerical implementation for coarse-grained molecular models. J Chem Phys. 2008; 128(24):244115. PMC: 2671180. DOI: 10.1063/1.2938857. View

16.

Theisen K, Zhmurov A, Newberry M, Barsegov V, Dima R . Multiscale modeling of the nanomechanics of microtubule protofilaments. J Phys Chem B. 2012; 116(29):8545-55. DOI: 10.1021/jp212608f. View

17.

Wagner J, Dama J, Durumeric A, Voth G . On the representability problem and the physical meaning of coarse-grained models. J Chem Phys. 2016; 145(4):044108. DOI: 10.1063/1.4959168. View

18.

Poblete S, Bottaro S, Bussi G . A nucleobase-centered coarse-grained representation for structure prediction of RNA motifs. Nucleic Acids Res. 2017; 46(4):1674-1683. PMC: 5829650. DOI: 10.1093/nar/gkx1269. View

19.

Katkar H, Davtyan A, Durumeric A, Hocky G, Schramm A, De La Cruz E . Insights into the Cooperative Nature of ATP Hydrolysis in Actin Filaments. Biophys J. 2018; 115(8):1589-1602. PMC: 6260209. DOI: 10.1016/j.bpj.2018.08.034. View

20.

Lee J, Iverson T, Dima R . Molecular investigations into the mechanics of actin in different nucleotide states. J Phys Chem B. 2010; 115(1):186-95. DOI: 10.1021/jp108249g. View