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Computer modeling and molecular dynamics simulations of ligand bound complexes of bovine angiogenin: Dinucleotide topology at the active site of RNase a family proteins
Author(s) -
Madhusudhan M.S.,
Sanjeev B.S.,
Vishveshwara S.
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.1120
Subject(s) - angiogenin , rnase p , molecular dynamics , ligand (biochemistry) , topology (electrical circuits) , chemistry , active site , computational biology , biology , genetics , rna , biochemistry , enzyme , computational chemistry , gene , mathematics , receptor , combinatorics , angiogenesis
We have undertaken the modeling of substrate‐bound structures of angiogenin. In our recent study, we modeled the dinucleotide ligand binding to human angiogenin. In the present study, the substrates CpG, UpG, and CpA were docked onto bovine angiogenin. This was achieved by overcoming the problem of an obstruction to the B1 site by the C‐terminus and identifying residues that bind to the second base. The modeled complexes retain biochemically important interactions. The docked models were subjected to 1 ns of molecular dynamics, and structures from the simulation were refined by using simulated annealing. Our models explained the enzyme's specificity for both B1 and B2 bases as observed experimentally. The nature of binding of the dinucleotide substrate was compared with that of the mononucleotide product. The models of these complexes were also compared with those obtained earlier with human angiogenin. On the basis of the simulations and annealed structures, we came up with a consensus topology of dinucleotide ligands that binds to human and bovine angiogenins. This dinucleotide conformation can serve as a starting model for ligand‐bound complex structures for RNase A family of proteins. We demonstrated this capability by generating the complex structure of CpA bound to eosinophil‐derived neurotoxin (EDN) by fitting the consensus topology of CpA to the crystal structure of native EDN. Proteins 2001;45:30–39. © 2001 Wiley‐Liss, Inc.