2 3Authors of CoMFA publications should consider the most important facts and prerequisites of 3D QSAR analyses and should publish a minimal set of information on their results, following these recommendations [I, 21: Selection of starting geometries.Especially in the case of flexible molecules authors should rationalize their choice by describing the approach used. In general, conformations of flexible drug molecules, adopted e.g. in vacuum, in solution, or in the crystal, are not necessarily similar to those required at a protein binding site. The conformations should be selected in a way to represent -to the best knowledge -the conditions under which the system was studied. In any case, the authors should give some ideas why the molecules in the data set were selected in these particular conformations [3 -61. Methods of geometry optimization of 3D structures.Starting structures obtained from model building or from any other source, including experimentally determined structures (e.g. X-ray structures, structures derived from NOE information, see section I), are in most cases optimized by some kind of molecular mechanics or quantum chemical approach. A documentation of the method (e.g. MM2, MAXIMIN, etc.) and its parametrization is required. It should be described whether the optimization has been performed including or ignoring Coulombic terms. If atom types not present in a standard force field implementation have been considered it should be mentioned how they were incorporated into the optimization.For quantum chemical optimization techniques, the authors should describe which methods have been applied (e.g. semiempirical methods such as CNDO, MNDO, AMI, PM3, PCILO, etc., or ab initio methods) and which convergence criteria have been set. For geometries obtained from ab initio calculations, the basis set should be given.Information about the quality of the structural data is important. Due to the functional forms of the fields, the CoMFA approach is very sensitive to small variations in geometry. If, e.g. the convergence criteria are too loosely set, different geometries will be obtained for identical portions of structural analogs, only because the next local minimum has not been reached. This will result in small RMS deviations which cause corresponding variances in the CoMFA fields [5, 61. 1 Charges used in CoMFA.A list of atomic charges is required for the calculation of electrostatic fields within CoMFA. The technique used in the analysis should be given together with the formal overall charge of the molecule (e.g. the protonation state). Some proof of consistency among the different methods is highly recommended IS]. Description of alignment criteria, grid spacing, and size of the CoMFA lattice and probe atodprobe charge used.Information about the alignment of the molecules is one of the most important criteria to decide on the quality of a 3D QSAR study. Accordingly, it should be clearly stated whether the alignment is based on experimental evidence or on hypothetical assumptions. Any computational ...
Ujber d i e Absorpt ionsspeJclren der Pr*aseodyrnsalxc und ihre Zeemaneff'elcte V o n Atj'red X e r x (Mit ti Figuren) I. EinleitungDie Linienspektren, die die Ionen der Seltenen Erden in ihren festen Verbiudungen in Absorption zeigen, sind wegen ihrer groBen Scharfe, die besonders bei tiefen Temperaturen teilweise die Scharfe yon Gaslinien erreicht, Gegenstand zahlreicher Untersuchungen gewesen '7 %). Die Moglichkeit solcher linienhafter Absorptionsspektrsn ist offenbar an das Vorhandensein unvollstandiger Elektronenschalen im Atom (bei den Seltenen Erden 4 f ) gebunden, die gegen Storungen von auBen durch stabile Elektronenkonfignrationen geschiitzt siud (Bs, 5p). Scharfe Linien treten nur dann auf, wenn die absorbierenden Elektronen die 4f-Schale nicht verlassen 3). Will man nun GesetzmaBigkeiten in diesen Spektren aufsuchen, SO scheint es am aussichtsreichsten , solclie Elemente zu nntersuchen, bei denen die 4f-Schale den einfachsten Aufbau hat, d. h. nur wenige Elektronen enthglt. Nur eilz 4f-Elektron enthalt das Cer, doch gibt es fiir dieses eine Elektron n u r einen Dublett-Term 2F in der 4j'-Schale4). Alle anderen Terme fiihren das Elektron aus dieser Schale heraus, und die Energiedifferenz der Dublettkomponenten selbst ist so kleiu, daB der Ubergang ins ferne Ultrarot fallen wiirde. Der fibergang von 4f nach 5 d (oder 6s) gibt AnlaB zu den im Ultravioletten gelegenen diffusen Banden des Ce+++-Ions 3). Das nlchsteinfache System, mit zwei Elektronen in der 4j'-Schale, ist das Praseodym, dessen sichtbares Spektrum in der vorliegenden Arbeit eingehend untersucht wird.Es wurden Salze aus verschiedenen Kristallsystemen untersucht und die auftretenden transversalen Zeemaneffekte gemessen, wobei immer die moglichen Orientierungen des Kristalls zum Magnetfeld und zum Lichtstrahl beriicksichtigt wurden. Auf das regullre Kristallsystem muRte leider verzichtet werden, da keine kubischen Salze oder Mineralien des Praseodyms bekannt sind. Auch Versuche, Praseodym in geniigender Konzentretion in kubische Salze einzulagern, verliefen erfolglos.
A representative range of pyrimidine nucleoside analogues that are known to inhibit herpes simplex virus (HSV) replication have been used to construct receptor binding site models for the varicella-zoster virus (VZV) thymidine kinase (TK) and human TK1. Given a set of interacting ligands, superimposed in such a manner as to define a pharmacophore, the pseudoreceptor modelling technique Yak provides a means of building binding site models of macromolecules for which no three-dimensional experimental structures are available. Once the models have been evaluated by their ability to reproduce experimental binding data [Vedani et al., J. Am. Chem. Soc., 117 (1995) 4987], they can be used for predictive purposes. Calculated and experimental values of relative binding affinity are compared. Our models suggest that the substitution of one residue may be sufficient to determine ligand subtype affinity.
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