A Descriptive Analysis of Populations of Three-Dimensional Structures Calculated from Primary Sequences of Proteins by Osiris

Abstract

Among different ab initio approaches to calculate 3D-structures of proteins out of primary sequences, a few are using restricted dihedral spaces and empirical equations of energy as is OSIRIS. All those approaches were calibrated on a few proteins or fragments of proteins. To optimize the calculation over a larger diversity of structures, we need first to define for each sequence what are good conditions of calculations in order to choose a consensus procedure fitting most 3D-structures best. This requires objective classification of calculated 3D-structures. In this work, populations of avian and bovine pancreatic polypeptides (APP, BPP) and of calcium-binding protein (CaBP) are obtained by varying the rate of the angular dynamics of the second step of OSIRIS. Then, 3D-structures are clustered using a nonhierarchical method, SICLA, using rmsd as a distance parameter. A good clustering was obtained for four subpopulations of APP, BPP and CaBP. Each subpopulation was characterized by its barycenter, relative frequency and dispersion. For the three alpha-helix proteins, after the step 1 of OSIRIS, most secondary structures were correct but molecules have a few atomic contacts. Step 2, i.e., the angular dynamics, resolves those atomic contacts and clustering demonstrates that it generates subpopulations of topological conformers as the barycenter topologies show.

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

“…The first step of OSIRIS is used in the present study since it is sufficient to correctly determine most secondary structures of different ␣-helix proteins (32). Briefly, the primary sequence of the peptide is introduced and 179 pairs of ⌽ and angles are succes- …”

“…Statistical analysis of the predicted structures of VIP and VIP analogs was made using the SICLA program (32). This procedure starts from n ϫ n distance tables calculated from the local root mean square distances of all pairs of structures obtained using different E mvi () values.…”

“…The clustering procedure used in SICLA is an automatic nonhierarchical classification that compares pairs of structures (34,35). This procedure is described in detail elsewhere (32). From the clustering of structures calculated with different values, a mean distance between the central structure and the others is obtained.…”

Molecular Determinants of the Interaction Between the C‐Terminal Domain of Alzheimer's β‐Amyloid Peptide and Apolipoprotein E α‐Helices

“…The total conformational energy is calculated as the sum of Van der Waals and electrostatic interactions, from the torsional potential energy and hydrophobic interactions quantified using an empirical equation for the free energy of solvation (Lins and Brasseur, 1995). Use of this corrective term in the energy field allows us to take water molecules into account implicitly and thus to obtain a better structure, as demonstrated for small molecules (Lins et al, 1996) and for the folding of small soluble proteins (Brasseur, 1995 ; Benhabiles et al, 1998).…”

The solvation concept approached by lipophily

“…Diverse methods of prediction of tridimensional structures of proteins were recently published [56][57][58][59][60][61]. They share the fact that, in addition to usual energetic terms describing the steric repulsion, the electrostatic interactions and the formation of hydrogen bonds, a term simulating solvation effects is added.…”