title: Molecular dynamics simulations of isoleucine-release pathway in GAF domain of N-CodY from Bacillus Subtilis.
abstract: The GAF domain located in the N-terminal motifs of CodY (N-CodY) is responsible for increasing the affinity of CodY to its target sites on DNA by its interaction with the branched chain amino acids (BCAAs) involving isoleucine, leucine and valine. The study of the interaction of GAF domain with isoleucine gains much attention in recent years, but the mechanism of isoleucine release still remains unclear. In this paper, a conventional molecular dynamics (MD) and force probe molecular dynamics (FPMD) simulations have been performed with the aim to understand how the isoleucine ligand escapes from the GAF domain of N-CodY from Bacillus subtilis. The MD results reveal that the ligand release is a gradual process, which is accompanied by the movement of the loop between β3 and β4. During the periods of ligand escaping from the bottom to the top of binding pocket, isoleucine forms hydrogen bonds one after another with series of residues, such as ARG61, THR96, PHE98, VAL100, GLU101 and ASN102, under the mediation of hydrophobic contacts. The FPMD results show that the easiest way to pull ligand out of the cavity is along x direction (i.e. the direction is opposite to MET62).
authors.affiliation: Key Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165, China. lingbaoping@yahoo.com.cn
authors.forename: Baoping
authors.initials: B
authors.lastname: Ling
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.forename: Siwei
authors.initials: S
authors.lastname: Bi
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Jing
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Wang
mesh_terms: D001412:Bacillus subtilis / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D007532:Isoleucine / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D014157:Transcription Factors; D007532:Isoleucine
keywords: Bacillus subtilis; Force probe molecular dynamics; GAF domain; Molecular dynamics simulations; N-CodY