title: Molecular Environment Modulates Conformational Differences between Crystal and Solution States of Human β-Defensin 2.
abstract: Human β-defensin 2 is a cysteine-rich antimicrobial peptide. In the crystal state, the N-terminal segment (residues 1-11) exhibits a helical conformation. However, a truncated form, with four amino acids removed from the N-terminus, adopts nonhelical conformations in solution, as shown by NMR. To explore the molecular origins of these different conformations, we performed Hamiltonian replica exchange molecular dynamics simulations of the peptide in solution and in the crystal state. It is found that backbone hydration and specific protein-protein interactions are key parameters that determine the peptide conformation. The helical conformation in the crystal state mainly arises from reduced hydration as well as a salt bridge between the peptide and a symmetry-related neighboring monomer in the crystal. When the extent of hydration is reduced and the salt bridge is reintroduced artificially, the peptide is successfully folded back to the helical conformation in solution. The findings not only shed light on the development of accurate force field parameters for protein molecules but also provide practical guidance in the design of functional proteins and peptides.
authors.affiliation: Singapore Eye Research Institute , 11 Third Hospital Avenue, #06-00, Singapore 168751.|Bioinformatics Institute (A*-STAR) , 30 Biopolis Street, #07-01 Matrix, Singapore 138671.
authors.forename: Jianguo
authors.identifier: 0000-0002-5544-6451
authors.initials: J
authors.lastname: Li
authors.affiliation: Bioinformatics Institute (A*-STAR) , 30 Biopolis Street, #07-01 Matrix, Singapore 138671.
authors.forename: Zhongqiao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Singapore Eye Research Institute , 11 Third Hospital Avenue, #06-00, Singapore 168751.|Department of Ophthalmology, National University of Singapore , Singapore 119074.|School of Chemical and Biomedical Engineering, Nanyang Technological University , Singapore 637459.
authors.forename: Roger
authors.initials: R
authors.lastname: Beuerman
authors.affiliation: Singapore Eye Research Institute , 11 Third Hospital Avenue, #06-00, Singapore 168751.|Bioinformatics Institute (A*-STAR) , 30 Biopolis Street, #07-01 Matrix, Singapore 138671.|School of Biological Sciences, Nanyang Technological University , Singapore 637551.|Department of Biological Sciences, National University of Singapore , Singapore 117543.
authors.forename: Chandra
authors.initials: C
authors.lastname: Verma
mesh_terms: D003460:Crystallization; D006801:Humans; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D012996:Solutions; D023083:beta-Defensins / Q000737:chemistry*
chemical_list: C106641:DEFB4A protein, human; D012996:Solutions; D023083:beta-Defensins