Calculation of protein backbone geometry from alpha- XXXX coordinates based on peptide-group dipole alignment.

@entity535 @entity505 @entity291 @entity3884
An algorithm is proposed for the conversion of a virtual-bond polypeptide chain (connected C alpha atoms) to an all-atom backbone, based on determining the most extensive @entity3884 -bond network between the peptide groups of the backbone, while maintaining all of the backbone atoms in energetically feasible conformations. @entity3884 bonding is represented by aligning the peptide-group dipoles. These peptide groups are not contiguous in the @entity535 sequence. The first dipoles to be aligned are those that are both sufficiently close in space to be arranged in approximately linear arrays termed dipole paths. The criteria used in the construction of dipole paths are: to assure good alignment of the greatest possible number of dipoles that are close in space; to optimize the electrostatic interactions between the dipoles that belong to different paths close in space; and to avoid locally unfavorable @entity535 residue conformations. The equations for dipole alignment are solved separately for each path, and then the remaining single dipoles are aligned optimally with the electrostatic field from the dipoles that belong to the dipole-path network. A least-squares minimizer is used to keep the geometry of the alpha- @entity505 trace of the resulting backbone close to that of the input virtual-bond chain. This procedure is sufficient to convert the virtual-bond chain to a real chain; in applications to real systems, however, the final structure is obtained by minimizing the total ECEPP/2 (empirical conformational energy program for peptides) energy of the system, starting from the geometry resulting from the solution of the alignment equations. When applied to model alpha-helical and beta-sheet structures, the algorithm, followed by the ECEPP/2 energy minimization, resulted in an energy and backbone geometry characteristic of these alpha-helical and beta-sheet structures. Application to the alpha- @entity505 trace of the backbone of the crystallographic 5PTI structure of @entity291 pancreatic trypsin inhibitor, followed by ECEPP/2 energy minimization with C alpha-distance constraints, led to a structure with almost as low energy and root mean square deviation as the ECEPP/2 geometry analog of 5PTI, the best agreement between the crystal and reconstructed backbone being observed for the residues involved in the dipole-path network.
