title: Understanding the conformational flexibility and electrostatic properties of curcumin in the active site of rhAChE via molecular docking, molecular dynamics, and charge density analysis.
abstract: Acetylcholinesterase (AChE) is an important enzyme responsible for Alzheimer's disease, as per report, keto-enol form of curcumin inhibits this enzyme. The present study aims to understand the binding mechanism of keto-enol curcumin with the recombinant human Acetylcholinesterase (rhAChE) from its conformational flexibility, intermolecular interactions, charge density distribution, and the electrostatic properties at the active site of rhAChE. To accomplish this, a molecular docking analysis of curcumin with the rhAChE was performed, which gives the structure and conformation of curcumin in the active site of rhAChE. Further, the charge density distribution and the electrostatic properties of curcumin molecule (lifted from the active site of rhAChE) were determined from the high level density functional theory (DFT) calculations coupled with the charge density analysis. On the other hand, the curcumin molecule was optimized (gas phase) using DFT method and further, the structure and charge density analysis were also carried out. On comparing the conformation, charge density distribution and the electrostatic potential of the active site form of curcumin with the corresponding gas phase form reveals that the above said properties are significantly altered when curcumin is present in the active site of rhAChE. The conformational stability and the interaction of curcumin in the active site are also studied using molecular dynamics simulation, which shows a large variation in the conformational geometry of curcumin as well as the intermolecular interactions.
authors.affiliation: a Laboratory of Biocrystallography and Computational Molecular Biology, Department of Physics , Periyar University , Salem , 636 011 , India.
authors.forename: Kandasamy
authors.initials: K
authors.lastname: Saravanan
authors.affiliation: a Laboratory of Biocrystallography and Computational Molecular Biology, Department of Physics , Periyar University , Salem , 636 011 , India.
authors.forename: Chinnasamy
authors.initials: C
authors.lastname: Kalaiarasi
authors.affiliation: a Laboratory of Biocrystallography and Computational Molecular Biology, Department of Physics , Periyar University , Salem , 636 011 , India.
authors.forename: Poomani
authors.initials: P
authors.lastname: Kumaradhas
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D020816:Amino Acid Motifs; D020134:Catalytic Domain; D003474:Curcumin / Q000737:chemistry*; D058851:GPI-Linked Proteins / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D011789:Quantum Theory; D011994:Recombinant Proteins / Q000737:chemistry; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D058851:GPI-Linked Proteins; D011994:Recombinant Proteins; C548244:ACHE protein, human; D000110:Acetylcholinesterase; D003474:Curcumin
keywords: charge density distribution; keto-enol form of curcumin; molecular docking; molecular dynamics; recombinant human AChE