Computational Structural Biology: Successes, Future Directions, and Challenges

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2019 Feb 15

PMID 30759724

Citations 8

Authors

Ruth Nussinov

Chung-Jung Tsai

Amarda Shehu

Hyunbum Jang

Affiliations

Soon will be listed here.

Abstract

Computational biology has made powerful advances. Among these, trends in human health have been uncovered through heterogeneous 'big data' integration, and disease-associated genes were identified and classified. Along a different front, the dynamic organization of chromatin is being elucidated to gain insight into the fundamental question of genome regulation. Powerful conformational sampling methods have also been developed to yield a detailed molecular view of cellular processes. when combining these methods with the advancements in the modeling of supramolecular assemblies, including those at the membrane, we are finally able to get a glimpse into how cells' actions are regulated. Perhaps most intriguingly, a major thrust is on to decipher the mystery of how the brain is coded. Here, we aim to provide a broad, yet concise, sketch of modern aspects of computational biology, with a special focus on computational structural biology. We attempt to forecast the areas that computational structural biology will embrace in the future and the challenges that it may face. We skirt details, highlight successes, note failures, and map directions.

Citing Articles

Integrative modeling of diverse protein-peptide systems using CABS-dock.

Pulawski W, Kolinski A, Kolinski M PLoS Comput Biol. 2023; 19(7):e1011275.

PMID: 37405984 PMC: 10351741. DOI: 10.1371/journal.pcbi.1011275.

Integrating computational skills in undergraduate Microbiology curricula in developing countries.

Adenaike O, Olabanjo O, Adedeji A Biol Methods Protoc. 2023; 8(1):bpad008.

PMID: 37396465 PMC: 10310463. DOI: 10.1093/biomethods/bpad008.

Generating tertiary protein structures via interpretable graph variational autoencoders.

Guo X, Du Y, Tadepalli S, Zhao L, Shehu A Bioinform Adv. 2023; 1(1):vbab036.

PMID: 36700110 PMC: 9710582. DOI: 10.1093/bioadv/vbab036.

The Challenges of 21st Century Neurotoxicology: The Case of Neurotoxicology Applied to Nanomaterials.

Bencsik A, Lestaevel P Front Toxicol. 2022; 3:629256.

PMID: 35295119 PMC: 8915904. DOI: 10.3389/ftox.2021.629256.

Pandemic strategies with computational and structural biology against COVID-19: A retrospective.

Liu C, Lu C, Lin L Comput Struct Biotechnol J. 2021; 20:187-192.

PMID: 34900126 PMC: 8650801. DOI: 10.1016/j.csbj.2021.11.040.

References

Gardino A, Villali J, Kivenson A, Lei M, Liu C, Steindel P . Transient non-native hydrogen bonds promote activation of a signaling protein. Cell. 2009; 139(6):1109-18. PMC: 2891250. DOI: 10.1016/j.cell.2009.11.022. View

Villali J, Kern D . Choreographing an enzyme's dance. Curr Opin Chem Biol. 2010; 14(5):636-43. PMC: 2987738. DOI: 10.1016/j.cbpa.2010.08.007. View

Barr D, Oashi T, Burkhard K, Lucius S, Samadani R, Zhang J . Importance of domain closure for the autoactivation of ERK2. Biochemistry. 2011; 50(37):8038-48. PMC: 3172398. DOI: 10.1021/bi200503a. View

Resasco D, Gao F, Morgan F, Novak I, Schaff J, Slepchenko B . Virtual Cell: computational tools for modeling in cell biology. Wiley Interdiscip Rev Syst Biol Med. 2011; 4(2):129-40. PMC: 3288182. DOI: 10.1002/wsbm.165. View

Tyagi M, Hashimoto K, Shoemaker B, Wuchty S, Panchenko A . Large-scale mapping of human protein interactome using structural complexes. EMBO Rep. 2012; 13(3):266-71. PMC: 3296913. DOI: 10.1038/embor.2011.261. View

Russel D, Lasker K, Webb B, Velazquez-Muriel J, Tjioe E, Schneidman-Duhovny D . Putting the pieces together: integrative modeling platform software for structure determination of macromolecular assemblies. PLoS Biol. 2012; 10(1):e1001244. PMC: 3260315. DOI: 10.1371/journal.pbio.1001244. View

Cowan A, Moraru I, Schaff J, Slepchenko B, Loew L . Spatial modeling of cell signaling networks. Methods Cell Biol. 2012; 110:195-221. PMC: 3519356. DOI: 10.1016/B978-0-12-388403-9.00008-4. View

Nussinov R, Tsai C . Allostery in disease and in drug discovery. Cell. 2013; 153(2):293-305. DOI: 10.1016/j.cell.2013.03.034. View

Ward R, Anderton M, Ashton S, Bethel P, Box M, Butterworth S . Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR). J Med Chem. 2013; 56(17):7025-48. DOI: 10.1021/jm400822z. View

10.

Baspinar A, Cukuroglu E, Nussinov R, Keskin O, Gursoy A . PRISM: a web server and repository for prediction of protein-protein interactions and modeling their 3D complexes. Nucleic Acids Res. 2014; 42(Web Server issue):W285-9. PMC: 4086120. DOI: 10.1093/nar/gku397. View

11.

Gursoy G, Xu Y, Kenter A, Liang J . Spatial confinement is a major determinant of the folding landscape of human chromosomes. Nucleic Acids Res. 2014; 42(13):8223-30. PMC: 4117743. DOI: 10.1093/nar/gku462. View

12.

Chen B . VASP-E: specificity annotation with a volumetric analysis of electrostatic isopotentials. PLoS Comput Biol. 2014; 10(8):e1003792. PMC: 4148194. DOI: 10.1371/journal.pcbi.1003792. View

13.

Nussinov R, Jang H, Tsai C . The structural basis for cancer treatment decisions. Oncotarget. 2014; 5(17):7285-302. PMC: 4202123. DOI: 10.18632/oncotarget.2439. View

14.

Nussinov R, Tsai C, Liu J . Principles of allosteric interactions in cell signaling. J Am Chem Soc. 2014; 136(51):17692-701. PMC: 4291754. DOI: 10.1021/ja510028c. View

15.

Nussinov R . Advancements and challenges in computational biology. PLoS Comput Biol. 2015; 11(1):e1004053. PMC: 4287606. DOI: 10.1371/journal.pcbi.1004053. View

16.

Fetics S, Guterres H, Kearney B, Buhrman G, Ma B, Nussinov R . Allosteric effects of the oncogenic RasQ61L mutant on Raf-RBD. Structure. 2015; 23(3):505-516. PMC: 7755167. DOI: 10.1016/j.str.2014.12.017. View

17.

Weiner A, Hsieh T, Appleboim A, Chen H, Rahat A, Amit I . High-resolution chromatin dynamics during a yeast stress response. Mol Cell. 2015; 58(2):371-86. PMC: 4405355. DOI: 10.1016/j.molcel.2015.02.002. View

18.

Nussinov R, Muratcioglu S, Tsai C, Jang H, Gursoy A, Keskin O . The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas. Mol Cancer Res. 2015; 13(9):1265-73. PMC: 4572916. DOI: 10.1158/1541-7786.MCR-15-0165. View

19.

Echeverria I, Liu Y, Gabelli S, Amzel L . Oncogenic mutations weaken the interactions that stabilize the p110α-p85α heterodimer in phosphatidylinositol 3-kinase α. FEBS J. 2015; 282(18):3528-42. PMC: 4573839. DOI: 10.1111/febs.13365. View

20.

Nussinov R, Tsai C . The Role of Allostery in the Termination of Second Messenger Signaling. Biophys J. 2015; 109(6):1080-1. PMC: 4576170. DOI: 10.1016/j.bpj.2015.07.007. View