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11.
聚类是芯片数据分析中被广泛使用的方法。未知基因的功能通常通过其与已知基因在不同生物状态下具有表达相似性来进行预测。然而,还未有人就这种通过表达相似性来进行功能注释的方法的可靠性进行评估。本文利用Gene Ontology对表达相似性和基因功能相似性的相关关系进行了全面的研究。研究表明,尽管表达谱的相似性和基因功能相似性之间有一定的依赖关系,但相关性较弱。在Gene Ontology的三大类中,相对生物过程和分子功能,基因表达谱的相似性更有助于细胞组分的注释。本文的研究结果对于基因功能的预测有一定的指导意义。 相似文献
12.
N. V. Grinberg T. M. Bibkov V. Ya. Grinberg V. B. Tolstoguzov 《Colloid and polymer science》1988,266(1):52-59
A study has been undertaken of stress relaxation in ovalbumin thermotropic gels with a concentration of 8–20%, depending on time and temperature of heating (respectively, 20–60 min, 70°–110°C), at pH 2.5–10.0. In all instances, the dependence of the initial gel elasticity modulus on heating has a single maximum. Gelation conditions corresponding to this maximum are considered optimal. Optimal gelation time is 30 min, regardless of pH. On the other hand, the optimal heating temperature depends on pH. To the right and left of the isoelectric point of protein (2.5pH<4.0 and 5.5G) of gels on heating conditions, pH and protein concentration (X
1,X
2,X
3,X
4), as well as on time of relaxation (t) may be generally described asG(X
1,X
1,X
1,X
1,t)=G
e(X
1,X
2,X
3,X
4)f(t), whereG
e is the equilibrium value of the elasticity modulus, and f(t) the relaxation function. Thus, a change in the parameters only affects the value of the equilibrium elasticity modulus, and exerts no effect on the relaxation time spectrum. For this reason, all the relaxation curves obtained may be transformed into two normalized relaxation functions:f(t)=f(t)/f(1)=G(X
1,X
2,X
3,X
4,t)/G(X
1,X
2,X
3,X
4, 1)Each of these normalized functions corresponds to one of the homologous groups. Rheological similarity of gels in each homologous group evidently points to their structural similarity. Invariance of the gel relaxationproperties with regard to protein concentration, leads to a concentration dependence of the equilibrium modulus at various pH values. These dependences are curvilinear on a double logarithmic scale. The slope of the curve exceeds 2 in the entire concentration interval studied. In other words, the dependences obtained cannot be described by the usual law of squares. On the other hand, they adequately match Hermans theoretical relation for a network formed by random association of identical polyfunctional particles without cyclization. This simple model evidently gives a true picture of the major regularities of thermotropic gelation for ovalbumin. An agreement between this theory and experiment was achieved for a protein concentration ofC
*=6.0±1.0% at the gel point regardless of pH. Invariance of gelpoint position with regards to pH demands further confirmation.List of symbols
T
h,t
h
heating temperature and time
-
T
h
*
,t
h
*
optimal heating temperature and time
-
C
protein concentration
-
C
*
protein concentration in gel-point
-
G
relaxation modulus
-
G
e
equilibrium modulus
-
f(t)
relaxation function
-
t
time of relaxation
-
f(t)
normalized relaxation function
-
fT
A
(t), f
B
(t)
normalized relaxation functions of groups A and B
-
G
1
T
h,t
h-reduced modulus
-
G
2
T
h,t
h, pH-reduced modulus
-
G
3
C-reduced modulus
-
b
1
T
h, th reduction parameter of modulus
-
b
2
pH reduction parameter of modulus
-
b
3
C reduction parameter of modulus
- Wg
gel-fraction 相似文献
13.
Paul Watson Peter Willett Valerie J. Gillet Marcel L. Verdonk 《Journal of computer-aided molecular design》2001,15(9):835-857
A knowledge-based method for calculating the similarity of functional groups is described and validated. The method is based on experimental information derived from small molecule crystal structures. These data are used in the form of scatterplots that show the likelihood of a non-bonded interaction being formed between functional group A (the `central group') and functional group B (the `contact group' or `probe'). The scatterplots are converted into three-dimensional maps that show the propensity of the probe at different positions around the central group. Here we describe how to calculate the similarity of a pair of central groups based on these maps. The similarity method is validated using bioisosteric functional group pairs identified in the Bioster database and Relibase. The Bioster database is a critical compilation of thousands of bioisosteric molecule pairs, including drugs, enzyme inhibitors and agrochemicals. Relibase is an object-oriented database containing structural data about protein-ligand interactions. The distributions of the similarities of the bioisosteric functional group pairs are compared with similarities for all the possible pairs in IsoStar, and are found to be significantly different. Enrichment factors are also calculated showing the similarity method is statistically significantly better than random in predicting bioisosteric functional group pairs. 相似文献
14.
Robert P. Apaya Baldo Lucchese Sarah L. Price J.G. Vinter 《Journal of computer-aided molecular design》1995,9(1):33-43
Summary Ligands which bind to a specific protein binding site are often expected to have a similar electrostatic environment which complements that of the binding site. One method of assessing molecular electrostatic similarity is to examine the possible overlay of the maxima and minima in the electrostatic potential outside the molecules and thereby match the regions where strong electrostatic interactions, including hydrogen bonds, with the residues of the binding site may be possible. This approach is validated with accurate calculations of the electrostatic potential, derived from a distributed multipole analysis of an ab initio charge density of the molecule, so that the effects of lone pair and -electron density are correctly included. We have applied this method to the phosphodiesterase (PDE) III substrate adenosine-3,5-cyclic monophosphate (cAMP) and a range of nonspecific and specific PDE III inhibitors. Despite the structural variation between cAMP and the inhibitors, it is possible to match three or four extrema to produce relative orientations in which the inhibitors are sufficiently sterically and electrostatically similar to the natural substrate to account for their affinity for PDE III. This matching of extrema is more apparent using the accurate electrostatic models than it was when this approach was first applied, using semiempirical point charge models. These results reinforce the hypothesis of electrostatic similarity and give weight to the technique of extrema matching as a useful tool in drug design. 相似文献
15.
Summary Electrostatic and structural properties of a set of -lactam, -lactam and nonlactam compounds have been analyzed and compared with those of a model of the natural substrate d-alanyl-d-alanine for the carboxy- and transpeptidase enzymes. This first comparison of the electrostatic properties has been based on a distributed multipole analysis of high-quality ab initio wave functions of the substrate and potential antibiotics. The electrostatic similarity of the substrate and active compounds is apparent, and contrasts with the electrostatic properties of the noninhibitors. This has been quantified to give a reasonable correlation with the MIC (Minimum Concentration for Inhibition) and with kinetic data (k2/K) in accordance with the model for interaction of the lactam compounds with dd-peptidase. These correlations provide a better prediction of antibacterial activity than purely structural criteria. 相似文献
16.
This paper applies discrete wavelet transform (DWT) with various protein substitution models to find functional similarity of proteins with low identity. A new metric, 'S' function, based on the DWT is proposed to measure the pair-wise similarity. We also develop a segmentation technique, combined with DWT, to handle long protein sequences. The results are compared with those using the pair-wise alignment and PSI-BLAST. 相似文献
17.
A straightforward discussion on how to generate molecular fields is developed within the postulates of quantum mechanics. The theoretical formalism points towards the generalization and extension of the well-known molecular field forms, associated to density function and electrostatic molecular potential (EMP), including another category of fields associated to quantum molecular similarity measures. The results show that the new formalism can be easily applied to obtain an unlimited number of new information about molecular behavior. 相似文献
18.
Comparative molecular similarity indices analysis (CoMSIA), a three-dimensional quantitative structure activity relationship (3D QSAR) paradigm, was used to examine the correlations between the calculated physicochemical properties and the in vitro activities (3'-processing and 3'-strand transfer inhibition) of a series of human immunodeficiency virus type 1 (HIV-1) integrase inhibitors. The training set consisted of 34 molecules from five structurally diverse classes: salicylpyrazolinones, dioxepinones, coumarins, quinones, and benzoic hydrazides. The data set was aligned using extrema of molecular electrostatic potentials (MEPs). The predictive ability of the resultant model was evaluated using a test set comprised of 7 molecules belonging to a different structural class of thiazepinediones. A CoMSIA model using an MEP-based alignment showed considerable internal as well external predictive ability (r2(cv) = 0.821, r2(pred) = 0.608 for 3'-processing; and r2(cv) = 0.759, r2(pred.) = 0.660 for 3'-strand transfer). 相似文献
19.
New 2D graphical representation of DNA sequences 总被引:5,自引:0,他引:5
We consider a 2D graphical representations of DNA sequences, which avoids loss of information associated with crossing and overlapping of the corresponding curve. We outline an approach, which is based on the construction of a three-component vector whose components are the normalized leading eigenvalues of the L/L matrices associated with DNA. The examination of similarities/dissimilarities among the coding sequences of the first exon of beta-globin gene of different species illustrates the utility of the approach. 相似文献
20.
Peptides represent an extensive class of biologically active molecules. They may be used as leads in the development of novel therapeutic agents provided the pharmacophoric information present within them can be translated into non-peptide analogs that lack the peptide backbone and are stable to proteolysis. This is the rationale for peptidomimetic drug design. Frequently, the -turn has been implicated as a conformation important for biological recognition of peptides. Empirical evidence from known peptidomimetics, coupled with a theoretical model of peptide binding and the observation that glycine and proline residues are common within the -turn, has suggested the design of molecules to mimic placement of between two and four of the side-chains. The moderate number of different -turn conformations, combined with the combinatoric nature of side-chain selection complicates the procedure. In this paper, cluster analysis has been used to classify the arrangement of C_ atoms about the various fragments of the -turn. Recombination of the observed patterns provides a general model for the -turn which may be used as an effective screen for potential peptidomimetic scaffolds in chemical databases. 相似文献