title: A molecular dynamics study based post facto free energy analysis of the binding of bovine angiogenin with UMP and CMP ligands.
abstract: Angiogenin is a protein belonging to the superfamily of RNase A. The RNase activity of this protein is essential for its angiogenic activity. Although members of the RNase A family carry out RNase activity, they differ markedly in their strength and specificity. In this paper, we address the problem of higher specificity of angiogenin towards cytosine against uracil in the first base binding position. We have carried out extensive nano-second level molecular dynamics(MD) computer simulations on the native bovine angiogenin and on the CMP and UMP complexes of this protein in aqueous medium with explicit molecular solvent. The structures thus generated were subjected to a rigorous free energy component analysis to arrive at a plausible molecular thermodynamic explanation for the substrate specificity of angiogenin.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: M S
authors.initials: MS
authors.lastname: Madhusudhan
authors.forename: S
authors.initials: S
authors.lastname: Vishveshwara
authors.forename: A
authors.initials: A
authors.lastname: Das
authors.forename: P
authors.initials: P
authors.lastname: Kalra
authors.forename: B
authors.initials: B
authors.lastname: Jayaram
mesh_terms: D000818:Animals; D002417:Cattle; D003568:Cytidine Monophosphate / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity; D013816:Thermodynamics; D014542:Uridine Monophosphate / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008024:Ligands; D014542:Uridine Monophosphate; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D003568:Cytidine Monophosphate