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Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation\u2010mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein\u2010protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP\u2010dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket\u2010detecting screenings and a quantitative hot\u2010spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the \u03b14\u2010\u03b25\u2010\u03b15 face) with energetic \u201chot\u2010spot\u201d areas, which could be used to search for modulators of protein\u2010protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs.<\/jats:p>","DOI":"10.1002\/minf.201700031","type":"journal-article","created":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T15:46:47Z","timestamp":1497023207000},"source":"Crossref","is-referenced-by-count":4,"title":["Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations"],"prefix":"10.1002","volume":"36","author":[{"given":"Xiao\u2010Yu","family":"Qing","sequence":"first","affiliation":[{"name":"Laboratory for Biomolecular Modelling, and Laboratory for Biomolecular Modelling and design, the Chemistry Department KULeuven  Celestijnenlaan 200G-bus2403 Heverlee Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Steenackers","sequence":"additional","affiliation":[{"name":"Centre of Microbial and Plant Genetics KULeuven  Kasteelpark Arenberg 20-bus2460 Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Venken","sequence":"additional","affiliation":[{"name":"Flemish Institute for Technological Research, VITO  Boeretang 200 2400 MOL Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"De\u2005Maeyer","sequence":"additional","affiliation":[{"name":"Laboratory for Biomolecular Modelling, and Laboratory for Biomolecular Modelling and design, the Chemistry Department KULeuven  Celestijnenlaan 200G-bus2403 Heverlee Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnout","family":"Voet","sequence":"additional","affiliation":[{"name":"Laboratory for Biomolecular Modelling, and Laboratory for Biomolecular Modelling and design, the Chemistry Department KULeuven  Celestijnenlaan 200G-bus2403 Heverlee Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"375","volume":"15","author":"Mullard A.","year":"2016","journal-title":"Nat. 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