Energy parameters in polypeptides. 10. Improved geometrical parameters and nonbonded interactions for use in the ECEPP/3 algorithm, with application to proline-containing peptides

Abstract

Some of the parameters that are used in the computer program ECEPP (Empirical Conformational Energy Program for Peptides) to describe the geometry of amino acid residues and the potential energy of interactions have been updated. The changes are based on recently available experimental information. The most signifcant changes improve the geometry and the interactions of prolyl and hydroxyprolyl residues, on the basis of crystallographic structural data. The structure of the pyrrolidine ring has been revised to correspond to the experimentally determined extent of out-of-plane puckering of the five-membered ring. The geometry of the peptide group preceding a Pro residue has also been altered. The parameters for nonbonded interactions involving the C6 and H* atoms of Pro and Hyp have been modified. Use of the revised parameters provides improvements in the computed minimum-energy conformations of peptides containing the Pro-Pro and Ala-Pro sequences. In particular, it is demonstrated that an a-helix-like conformation of a residue preceding Pro is now only of moderately high energy, and thus it is an accessible state. This result corroborates the observed occurrence of Pro residues in kinked a-helices in globular proteins. The structure of the poly(G1y-PrePro) triple helix, a computational model for collagen structure, has been recomputed. The validity of previous computations for this model structure has been confirmed. The refinement of the computed interactions has provided a new general model structure to be used for future computations on collagen-like polypeptides.

Evolution and Physics in Comparative Protein Structure Modeling

“…This hope is underpinned by the recent improvements in molecular mechanics force fields 37,39,40 and the ever increasing time scale of the molecular dynamics simulations. 41 Nevertheless, attempts to improve comparative models by molecular dynamics simulations have not yet been successful.…”

New optimization method for conformational energy calculations on polypeptides: Conformational space annealing

“…9 The residue geometry and the interatomic interaction energies used were those in the revised version, 10 ECEPPr3, of the Empirical Conformational Energy Program for Peptides. In ECEPPr3 each conformation of a polypeptide is represented by a set of Ä 4 dihedral angles , .…”

Structure-based design and screening of inhibitors for an essential bacterial GTPase, Der

“…13 The 3D structure of Der has been regularized with the ECEPP/3 force field 18 in order to adjust X-ray coordinates to standard polypeptide geometry. GD1 was superimposed with auxiliary templates of active and inactive states; that is, crystal structures of Ras in complex with GTP (PDB ID: 121P) 19 and GDP (PDB ID: 4Q21), 20 respectively, and the ligand molecules were transferred from auxiliary templates into GD1 (Figure 1).…”