Chicken liver bile acid binding protein (cL-BABP) crystallizes with water molecules in its binding site. To obtain insights on the role of internal water, we performed two 100 ns molecular dynamics (MD) simulations in explicit solvent for cL-BABP, as apo form and as a complex with two molecules of cholic acid, and analyzed in detail the dynamics properties of all water molecules. The diffusion coefficients of the more persistent internal water molecules are significantly different from the bulk, but similar between the two protein forms. A different number of molecules and a different organization are observed for apo- and holo-cL-BABP. Most water molecules identified in the binding site of the apo-crystal diffuse to the bulk during the simulation. In contrast, almost all the internal waters of the holo-crystal maintain the same interactions with internal sidechains and ligands, which suggests they have a relevant role in protein-ligand molecular recognition. Only in the presence of these water molecules we were able to reproduce, by a classical molecular docking approach, the structure of the complex cL-BABP::cholic acid with a low ligand root mean square deviation (RMSD) with respect to its reference positioning. Literature data reported a conserved pattern of hydrogen bonds between a single water molecule and three amino acid residues of the binding site in a series of crystallized FABP. In cL-BABP, the interactions between this conserved water molecule and the three residues are present in the crystal of both apo- and holo-cL-BABP but are lost immediately after the start of molecular dynamics

Structural and dynamic roles of permanent water molecules in ligand molecular recognition by chicken liver bile acid binding protein / P. Ricchiuto, A. Guerini Rocco, E. Gianazza, D. Corrada, T. Beringhelli, I. Eberini. - In: JOURNAL OF MOLECULAR RECOGNITION. - ISSN 0952-3499. - 21:5(2008), pp. 347-353.

Structural and dynamic roles of permanent water molecules in ligand molecular recognition by chicken liver bile acid binding protein

P. Ricchiuto
Primo
;
A. Guerini Rocco
Secondo
;
E. Gianazza;D. Corrada;T. Beringhelli
Penultimo
;
I. Eberini
Ultimo
2008

Abstract

Chicken liver bile acid binding protein (cL-BABP) crystallizes with water molecules in its binding site. To obtain insights on the role of internal water, we performed two 100 ns molecular dynamics (MD) simulations in explicit solvent for cL-BABP, as apo form and as a complex with two molecules of cholic acid, and analyzed in detail the dynamics properties of all water molecules. The diffusion coefficients of the more persistent internal water molecules are significantly different from the bulk, but similar between the two protein forms. A different number of molecules and a different organization are observed for apo- and holo-cL-BABP. Most water molecules identified in the binding site of the apo-crystal diffuse to the bulk during the simulation. In contrast, almost all the internal waters of the holo-crystal maintain the same interactions with internal sidechains and ligands, which suggests they have a relevant role in protein-ligand molecular recognition. Only in the presence of these water molecules we were able to reproduce, by a classical molecular docking approach, the structure of the complex cL-BABP::cholic acid with a low ligand root mean square deviation (RMSD) with respect to its reference positioning. Literature data reported a conserved pattern of hydrogen bonds between a single water molecule and three amino acid residues of the binding site in a series of crystallized FABP. In cL-BABP, the interactions between this conserved water molecule and the three residues are present in the crystal of both apo- and holo-cL-BABP but are lost immediately after the start of molecular dynamics
Bile acid binding protein; Calycin; Delaunay tessellation; Fatty acid binding protein; Internal water; Lipid binding protein; Molecular docking; Molecular dynamics
Settore CHIM/03 - Chimica Generale e Inorganica
Settore BIO/14 - Farmacologia
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/71517
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