Reaching New Levels of Realism in Modeling Biological Macromolecules in Cellular Environments

Overview

Journal J Mol Graph Model

Date 2013 Sep 17

PMID 24036504

Citations 26

Authors

Michael Feig

Yuji Sugita

Affiliations

Soon will be listed here.

Abstract

An increasing number of studies are aimed at modeling cellular environments in a comprehensive and realistic fashion. A major challenge in these efforts is how to bridge spatial and temporal scales over many orders of magnitude. Furthermore, there are additional challenges in integrating different aspects ranging from questions about biomolecular stability in crowded environments to the description of reactive processes on cellular scales. In this review, recent studies with models of biomolecules in cellular environments at different levels of detail are discussed in terms of their strengths and weaknesses. In particular, atomistic models, implicit representations of cellular environments, coarse-grained and spheroidal models of biomolecules, as well as the inclusion of reactive processes via reaction-diffusion models are described. Furthermore, strategies for integrating the different models into a comprehensive description of cellular environments are discussed.

Citing Articles

PEG-mCherry interactions beyond classical macromolecular crowding.

Haas-Neill L, Joron K, Lerner E, Rauscher S Protein Sci. 2025; 34(3):e5235.

PMID: 39968832 PMC: 11836898. DOI: 10.1002/pro.5235.

View of Crowding: Biomolecular Processes to Nanomaterial Design.

Rajput S, Panigrahy S, Nayar D ACS Omega. 2024; 9(28):29953-29965.

PMID: 39035939 PMC: 11256109. DOI: 10.1021/acsomega.4c03344.

Varying molecular interactions explain aspects of crowder-dependent enzyme function of a viral protease.

Ostrowska N, Feig M, Trylska J PLoS Comput Biol. 2023; 19(4):e1011054.

PMID: 37098073 PMC: 10162569. DOI: 10.1371/journal.pcbi.1011054.

Crowding within synaptic junctions influences the degradation of nucleotides by CD39 and CD73 ectonucleotidases.

Rahmaninejad H, Pace T, Chun B, Kekenes-Huskey P Biophys J. 2021; 121(2):309-318.

PMID: 34922916 PMC: 8790186. DOI: 10.1016/j.bpj.2021.12.013.

Computer-Aided Whole-Cell Design: Taking a Holistic Approach by Integrating Synthetic With Systems Biology.

Marucci L, Barberis M, Karr J, Ray O, Race P, de Souza Andrade M Front Bioeng Biotechnol. 2020; 8:942.

PMID: 32850764 PMC: 7426639. DOI: 10.3389/fbioe.2020.00942.

References

Samiotakis A, Cheung M . Folding dynamics of Trp-cage in the presence of chemical interference and macromolecular crowding. I. J Chem Phys. 2011; 135(17):175101. DOI: 10.1063/1.3656691. View

Wang Q, Cheung M . A physics-based approach of coarse-graining the cytoplasm of Escherichia coli (CGCYTO). Biophys J. 2012; 102(10):2353-61. PMC: 3353097. DOI: 10.1016/j.bpj.2012.04.010. View

McGuffee S, Elcock A . Diffusion, crowding & protein stability in a dynamic molecular model of the bacterial cytoplasm. PLoS Comput Biol. 2010; 6(3):e1000694. PMC: 2832674. DOI: 10.1371/journal.pcbi.1000694. View

Thanbichler M, Wang S, Shapiro L . The bacterial nucleoid: a highly organized and dynamic structure. J Cell Biochem. 2005; 96(3):506-21. DOI: 10.1002/jcb.20519. View

Zhou H . Influence of crowded cellular environments on protein folding, binding, and oligomerization: biological consequences and potentials of atomistic modeling. FEBS Lett. 2013; 587(8):1053-61. PMC: 3729036. DOI: 10.1016/j.febslet.2013.01.064. View

Li P, Banjade S, Cheng H, Kim S, Chen B, Guo L . Phase transitions in the assembly of multivalent signalling proteins. Nature. 2012; 483(7389):336-40. PMC: 3343696. DOI: 10.1038/nature10879. View

Hudder A, Nathanson L, Deutscher M . Organization of mammalian cytoplasm. Mol Cell Biol. 2003; 23(24):9318-26. PMC: 309675. DOI: 10.1128/MCB.23.24.9318-9326.2003. View

Heath A, Kavraki L, Clementi C . From coarse-grain to all-atom: toward multiscale analysis of protein landscapes. Proteins. 2007; 68(3):646-61. DOI: 10.1002/prot.21371. View

Ando T, Skolnick J . On the importance of hydrodynamic interactions in lipid membrane formation. Biophys J. 2013; 104(1):96-105. PMC: 3540244. DOI: 10.1016/j.bpj.2012.11.3829. View

10.

Rao J, Cruz L . Effects of confinement on the structure and dynamics of an intrinsically disordered peptide: a molecular-dynamics study. J Phys Chem B. 2013; 117(14):3707-19. DOI: 10.1021/jp310623x. View

11.

Tanizaki S, Clifford J, Connelly B, Feig M . Conformational sampling of peptides in cellular environments. Biophys J. 2007; 94(3):747-59. PMC: 2186233. DOI: 10.1529/biophysj.107.116236. View

12.

Hu C, Kokubo H, Lynch G, Bolen D, Pettitt B . Backbone additivity in the transfer model of protein solvation. Protein Sci. 2010; 19(5):1011-22. PMC: 2868243. DOI: 10.1002/pro.378. View

13.

Saxton M . Anomalous diffusion due to obstacles: a Monte Carlo study. Biophys J. 1994; 66(2 Pt 1):394-401. PMC: 1275707. DOI: 10.1016/s0006-3495(94)80789-1. View

14.

Qin S, Minh D, McCammon J, Zhou H . Method to Predict Crowding Effects by Postprocessing Molecular Dynamics Trajectories: Application to the Flap Dynamics of HIV-1 Protease. J Phys Chem Lett. 2010; 1(1):107-110. PMC: 2837415. DOI: 10.1021/jz900023w. View

15.

Gnatt A, Cramer P, Fu J, Bushnell D, Kornberg R . Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 A resolution. Science. 2001; 292(5523):1876-82. DOI: 10.1126/science.1059495. View

16.

Frembgen-Kesner T, Elcock A . Absolute protein-protein association rate constants from flexible, coarse-grained Brownian dynamics simulations: the role of intermolecular hydrodynamic interactions in barnase-barstar association. Biophys J. 2010; 99(9):L75-7. PMC: 2965997. DOI: 10.1016/j.bpj.2010.09.006. View

17.

Lapin A, Klann M, Reuss M . Multi-scale spatio-temporal modeling: lifelines of microorganisms in bioreactors and tracking molecules in cells. Adv Biochem Eng Biotechnol. 2010; 121:23-43. DOI: 10.1007/10_2009_53. View

18.

Thomas A, Elcock A . Direct observation of salt effects on molecular interactions through explicit-solvent molecular dynamics simulations: differential effects on electrostatic and hydrophobic interactions and comparisons to Poisson-Boltzmann theory. J Am Chem Soc. 2006; 128(24):7796-806. DOI: 10.1021/ja058637b. View

19.

Rauscher S, Pomes R . Molecular simulations of protein disorder. Biochem Cell Biol. 2010; 88(2):269-90. DOI: 10.1139/o09-169. View

20.

Postow L, Hardy C, Arsuaga J, Cozzarelli N . Topological domain structure of the Escherichia coli chromosome. Genes Dev. 2004; 18(14):1766-79. PMC: 478196. DOI: 10.1101/gad.1207504. View