Specificity and Selectivity in Protein-Ion Binding

蛋白质-离子结合的特异性和选择性

• 批准号: 9062465
• 负责人: JAY PONDER
• 金额: $ 29.14万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9062465
• 关键词: Acute; Adenine Nucleotides; Anions; Binding; Binding Proteins; Binding Sites; Biosensor; Cells; Charge; Chemistry; Computing Methodologies; Data; Development; Diagnostic; Disease; Drug Targeting; Electrostatics; Enzymes; Fingerprint; Free Energy; Goals; Health; Ions; Knowledge; Lead; Ligands; Link; Malignant Neoplasms; Mechanics; Metal Ion Binding; Metalloproteins; Metals; Modeling; Molecular; Molecular Models; Mutation; Nerve Degeneration; Penetration; Phosphoric Monoester Hydrolases; Phosphorylated Peptide; Phosphotransferases; Play; Positioning Attribute; Potential Energy; Process; Protein Engineering; Proteins; Public Health; Pyridoxal Phosphate; Regulation; Research; Shapes; Signal Transduction; Signaling Protein; Software Tools; Specificity; Structure; Surface; System; Theoretical Studies; Thermodynamics; Trace Elements; Transition Elements; base; chemical property; computer studies; computerized tools; design; divalent metal; driving force; experience; inorganic phosphate; molecular dynamics; molecular modeling; novel therapeutics; open source; physical property; quantum; src Homology Region 2 Domain; therapeutic protein; therapeutic target; water environment

 DESCRIPTION (provided by applicant): Ions are essential components of biomolecular systems. One third of all proteins contain metal ions as integral parts for structural or functiona purposes. Binding of negatively charged phosphate groups is ubiquitously involved in regulation, signal transduction and various other processes. Whereas is a plethora of experimental structural and thermodynamic information about protein-ion systems, our understanding of the mechanism for specific recognition and protein/ion selectivity remains elusive. Computational and theoretical studies of protein-ion systems using classical models are very challenging due to the lack of accurate and yet computationally tractable classical models for simulating ions in proteins. We propose to systematically investigate the binding of divalent metal ions and phosphate containing ligands to proteins using quantum mechanical calculations and classical molecular dynamics simulations. We will rigorously examine the different types of physical forces in protein-ion interactions using quantum mechanical energy decomposition, and develop a new classical model to accurately describe the physical interactions between ions and protein/water environment. With this new classical model, we will obtain quantitative understanding of the thermodynamic driving forces underlying the specificity and selectivity from molecular dynamics simulations. Given the fundamental importance of protein-ion binding, this research will have a broad impact on advancing our scientific knowledge about ions in biomolecular structure and functions. This research will also lead to computational methods and public software tools that will enable accurate prediction of protein-ion binding and ultimately design of new molecules and proteins targeting specific ions.