Ligand Binding: Molecular Mechanics
نویسندگان
چکیده
The force required to rupture the streptavidin-biotin complex was calculated here by computer simulations. The computed force agrees well with that obtained by recent single molecule atomic force microscope experiments. These simulations suggest a detailed multiple-pathway rupture mechanism involving five major unbinding steps. Binding forces and specificity are attributed to a hydrogen bond network between the biotin ligand and residues within the binding pocket of streptavidin. During rupture, additional water bridges substantially enhance the stability of the complex and even dominate the binding interactions. In contrast, steric restraints do not appear to contribute to the binding forces, although conformational motions were observed.
منابع مشابه
Molecular Dynamics Simulation and Free Energy Studies on the Interaction of Salicylic Acid with Human Serum Albumin (HSA)
Human serum albumin (HSA) is the most abundant protein in the blood plasma. Molecular dynamics simulations of subdomain IIA of HSA and its complex with salicylic acid (SAL) were performed to investigate structural changes induced by the ligand binding. To estimate the binding affinity of SAL molecule to subdomains IB and IIA in HSA protein, binding free energies were calculated using the Molecu...
متن کاملMolecular Modeling Studies on Vinblastine Binding Site of Tubulin for Antimitotic agents
Medicinal chemistry depends on many other disciplines ranging from organic chemistry andpharmacology to computational chemistry. Typically medicinal chemists use the moststraightforward ways to prepare compounds. The validation of any design project comes from thebiological testing.Studies of the binding site of vinblastine by a single cross—linking experiment identified it asbeing between resi...
متن کاملIsothermal Titration Calorimetry and Molecular Dynamics Simulation Studies on the Binding of Indometacin with Human Serum Albumin
Human serum albumin (HSA) is the most abundant protein in the blood plasma. Drug binding to HSA is crucial to study the absorption, distribution, metabolism, efficiency and bioavailability of drug molecules. In this study, isothermal titration calorimetry and molecular dynamics simulation of HSA and its complex with indometacin (IM) were performed to investigate thermodynamics parameters and th...
متن کاملInteraction of Human Serum Albumin with Ethyl 2-[2-(dimethylamino)-4-(4-nitrophenyl)-1,3-thiazole-5-yl]-2-oxoacetate as a Synthesized Ligand
The interaction of human serum albumin with Ethyl 2-[2-(dimethylamino)-4-(4-nitrophenyl)- 1,3-thiazole-5-yl]-2-oxoacetate was investigated by using isothermal titration UV-visible spectrophotometry in tris-buffer, pH 7.4. According to these results, it was found that there are a set of 4 binding sites for this ligand on HSA with positive cooperativity in the binding process. This thiazole deriv...
متن کاملDesign of protein-ligand binding based on the molecular-mechanics energy model.
While the molecular-mechanics field has standardized on a few potential energy functions, computational protein design efforts are based on potentials that are unique to individual laboratories. Here we show that a standard molecular-mechanics potential energy function without any modifications can be used to engineer protein-ligand binding. A molecular-mechanics potential is used to reconstruc...
متن کاملMolecular Docking Based on Virtual Screening, Molecular Dynamics and Atoms in Molecules Studies to Identify the Potential Human Epidermal Receptor 2 Intracellular Domain Inhibitors
Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Overexpression of HER2 usually causes malignant transformation of cells and is responsible for the breast cancer. In this work, the virtual screening, molecular docking, quantum mechanics and molecular dynamics methods were employed to study protein–ligand ...
متن کامل