A new addition to the structural bioinformatics toolbox: 3D models of short bioactive peptides from multiple sequences using feedback restrained molecular dynamics (FRMD).

Modem molecular biology techniques allow the use of new approaches for the 3D mapping of 1D information. Molecular biology techniques are capable of producing large amounts of 1D information (sequences) from a number of different sources (phage displays, ESTs, etc.). In this work, we present a technique that takes advantage of large sets of 1D information and increasingly available computer power to create 3D models. For the purpose of validation the technique is first applied to the modeling of an erythropoietin analog of known 3D structure from 1D information only. The technique is then used to model the immunoreactive region of echinococcus granulosus AgB based on phage raised mimotopes for which there is no previous structural information. The technique here presented is of general application to similar problems where 1D information is available and structure activity relationships (SAR) is needed.

Density functional study of isomerization of fluoro- and chloroformaldehyde radical cations.

Ab initio and density functional (DFT) calculations were performed on radical cations with the formula HXCO(+˙) (X = H, F, and CI) and their isomers XCOH(+˙) . Hartree-Fock, Møller-Plesset at second order (MP2), and quadratic configuration interaction including singles and doubles (QCISD) methods were employed for geometry optimizations at the ab initio level. Becke's 1988 and three-parameter exchange potentials, together with Vosko-Wilk-Nusair (VWN) and Lee-Yang-Paar (LYP) correlation potentials (BVWN, BLYP, and B3LYP) were used for the DFT calculations. HF and MPn isomerization energies are severely in error, mostly due to a bad description of the XHCO(+˙) cation radicals at the Hartree-Fock level, leading to oscillatory behavior of the perturbation series. QCISD methods, at least, are needed to obtain accurate results at the conventional ab initio level, even using large extended basis sets. B3LYP results are most similar to QCISD results for the isomerization energies of the three cation radicals. Parent neutral species are also described to a high degree of accuracy. B3LYP methods are faster than QCISD (and as exact as them) for all the cases studied here. MP2 methods, although giving incorrect results, are faster than B3LYP up to about 80 basis functions. For larger problems, B3LYP methods are faster. The best theoretical results obtained indicate that fluoro- and chloroformaldehyde cation radicals are less stable than their hydroxyfluoro- and hydroxychloromethylene isomers, the reverse situation than for the formaldehyde cation radical. The best values found in this article for the isomerization energy of XHCO(+˙) are -26 ± 2 kJ/mol (X = H), +37 ± 2 kJ/mol (X = F), and +28 ± 2 kJ/mol (X = CI). Ionization energies of 10.9, 12.3, and 11.4 eV are predicted for the XHCO species (X = H, F, CI). © 1996 by John Wiley & Sons, Inc.