Protein-protein interactions: Methods, databases, and applications in virus-host study

Table 1 List of some important computational methods of protein-protein interaction prediction along with their brief descriptions

Method	Description	Ref.
In silico two-hybrid (I2H)	The I2H method is based on the detection of direct physical associations between the interacting proteins and it relies on the presumption that in order to maintain the protein function reliable, the interacting proteins should go through coevolution	Pazos and Valencia[38]
Ortholog-based approach	It is a sequence-based approach that uses a pairwise local search algorithm to obtain the similarities between the query protein pairs and the known interaction pairs. It is dependent upon the homologous nature of the target proteins	Lee et al[39]
Gene fusion	Also known as Rosetta stone method. According to this method, some of the proteins with single domains fuse together in one organism and form a multi-domain protein in another organism	Enright et al[40]
Domain-pairs-based approach	This method predicts the interactions between proteins by the domain-domain interactions	Wojcik and Schächter[41]
Gene expression	An indirect way to predict PPIs. Based on the concept that the proteins translated from the genes that belong to the common expression profiling clusters more likely interact with each other than the proteins translated from the genes that belong to different clusters	Grigoriev[42]
Structure-based approaches	It predicts protein-protein interactions based on the structural similarity	Zhang et al[43]
Phylogenetic tree	This method predicts protein-protein interactions based on the concept that the interacting proteins show similarity in their evolution history	Sato et al[44]

PPI: Protein-protein interaction.

Table 2 List of popular protein-protein interaction databases with total numbers of interactions and last updated time

PPI database	URL	Total interactions	Last updated	Ref.
STRING	http://string-db.org/	> 2000 mio	2020	Szklarczyk et al[50]
BioGrid	http://thebiogrid.org/	1746922	2021	Oughtred et al[47]
HPIDB	https://hpidb.igbb.msstate.edu/index.html	69787	2019	Ammari et al[51]
MINT	https://mint.bio.uniroma2.it/	131695	2012	Zahiri et al[3] and Licata et al[55]
DIP	https://dip.doe-mbi.ucla.edu/dip/Main.cgi	81923	2017	Zahiri et al[3] and Salwinski et al[56]
IntAct	http://www.ebi.ac.uk/intact/	1130596	2020	Orchard et al[52]
HPRD	http://www.hprd.org/	41327	2010	Zahiri et al[3] and Keshava Prasad et al[57]

PPI: Protein-protein interaction; URL: Uniform resource locator.