The best comfa and comsia models presented values of r 2 ncv 0. Like other regression models, qsar regression models relate a set of predictor variables x to the potency of the response variable y, while classification qsar models relate the predictor variables to a categorical. There are several factors that affect the quality of the developed comfa and comsia. Apr 14, 2012 pneumocystis carinii is typically a nonpathogenic fungus found in the respiratory tract of healthy humans. The aim of comfa is to derive a correlation between the biological activity of a set of molecules and their 3d shape, electrostatic and hydrogen bonding characteristics. Converged communication turned into company knowledge. Comfa and comsia 3d qsar models for a series of some condensed thieno2,3dpyrimidin43hones with antihistaminic h1 activity. Unlike comsia, comfa does not have explicit hydrophobic and hydrogenbonding descriptors, which are assumed to be implicitly treated in the comfa steric and electrostatic fields, respectively.
The best comsia model showed a slightly better r cv 2 value i. Statistical analyses of comfa and comsia models different comfa and comsiabased 3dqsar models were generated using partial least square method pls by correlating biological activities of brd4 inhibitors in a training dataset with their. The fieldbased qsar models are based on comfa 1 and comsia 2, 3. The best predictions were obtained with a comfa model q20. After this division, we chec ked that both sets represent equally well the. Qsar, molecular docking and in silico pharmacokinetic prediction siddharth jitendrakumar modi, vithal madhvarao kulkarni department of pharmaceutical chemistry, poona college of pharmacy, bharati vidyapeeth deemed to be university, pune 411038, maharashtra, india. The predicted bioactivities of compounds designed by comfa and comsia. This directory enables the complete implementation of otemplate comfao, as introduced in the following references. Modeling study of phenylsulfonylfuroxan derivatives as pgp.
The predictive ability of comfa and comsia were determined using a test set of 15 imidazole derivatives giving predictive correlation coefficients of 0. Pdf comfa, comsia, knn mfa and docking studies of 1,2,4. Pdf comfa and comsia 3dqsar analysis of dmdp derivatives. Last year, gupta reported on studies based on comfa and comparative molecular similarity indices analysis comsia performed on a set of diverse.
The 3dqsar models demonstrated a reliable ability to predict the clogp of the active anticonvulsant enaminones, resulting in a q2 of 0. Comfa and comsia studies on hiv1 attachment inhibitors article in european journal of medicinal chemistry 455. The maps obtained by the new comsia approach are superior and easier to interpret whereas the comfa maps denote regions apart from the molecules where interactions with a putative environment are to be expected, the comsia maps highlight those regions within the area occupied by the ligand skeletons that require a particular physicochemical property important for activity. Comsia comparative molecular similarity index analysis comsia is a method developed recently as an extension of comfa. Graphical interpretation of the comfa and comsia models.
The 3d qsar models demonstrated a reliable ability to predict the clog p of the active anticonvulsant enaminones, resulting in a q 2 of 0. A combined approach of comfa, comsia and hqsar volume. Structural investigations of cxcr2 receptor antagonists by. In the comsia comparative molecular simi larity indices analysis approach 23 the same types of molecular fields are ap. Comfa and comsia methods were applied to build 3dqsar models using the structural parameters as independent variables and the binding free energy as the dependent variable to obtain the relationship between the binding free energy and molecular structure. The maps generated depict regions having scaled coefficients 80% favored or comfa, comsia and discotech author. Comparative molecular field analysis comfa and comparative molecular similarity indices analysis comsia were used to develop 3dqsar models of 64 pyridinonebased compounds. Pneumocystis carinii is typically a nonpathogenic fungus found in the respiratory tract of healthy humans. Quantitative structureactivity relationship wikipedia. While the chemical structures of remaining 4 molecules tyolophorine derivatives were retrieved from pubchem 18 in structure data file sdf format and converted to tripos mol2.
Introduction comfa comparative molecular field analysis is a 3d qsar technique based on data from known active molecules. Structureactivity relationships based on 3dqsar comfa. Department of pharmaceutical chemistry, school of pharmacy, addis ababa university, p. Pdf inhibitory activities of flavonoid derivatives against aldose reductase ar enzyme were modelled by using comfa, comsia and galahad methods.
Based on the comfa and comsia model, the visual 3d stdevcoeff contour maps were constructed as scalar products of coefficients and standard deviation, associated with each comfa or comsia column. The calculated binding free energies for 209 pcbs and bpha were used for modeling. Comfa, comsia, topomer comfa, hqsar, molecular docking. Template comfa generates single 3dqsar models that, for twelve of twelve biological targets, predict all chembltabulated affinities.
Accepted manuscript original article comfa, comsia, knn mfa and docking studies of 1,2,4oxadiazole deriv atives as potent caspase3 activators ankur. Comfa, comsia, hqsar and molecular docking analysis of iononebased chalcone derivatives as antiprostate cancer activity. All the comfa and comsia models fulfil the validation procedure proposed by golbraikh and. Original article quinazoline derivatives as anticancer agents. Jan 01, 2009 comfa and comsia were employed to generate models to define the specific structural and electrostatic features essential for enhanced binding to the putative gaba receptor. In the latter group, pcp occurs in approximately 80% of patients.
The comsia method includes more additional field properties they are steric, electrostatic, hydrophobic, hydrogen bond donor and hydrogen bond acceptor. As a result, factors affecting this class of compounds have been found to be steric and electrostatic effects. You can also choose file save aspdf, then choose pdfa from the save as type menu. To validate the contour maps of comfa and comsia, the molecular docking study between mtor protein pdb id. Modeling study of phenylsulfonylfuroxan derivatives as pgp inhibitors. The comsia model that included the seda fields presented good statistical parameters with a q 2 of 0. Each docking was minimized, using dockscore, the only purely molecular mechanics based scoring function employed in this study, and this minimized pose was then presented to each of the other scoring functions, which were either knowledge based or regression based. Truong b and mange ram yadav a a pharmacy department, faculty of technology and engineering, the m. Comfacomsia and pharmacophore modelling as a powerful. Last year, gupta reported on studies based on comfa and comparative molecular similarity indices analysis comsia performed on a set of. Bootstrapped analysis showed statistically significant and robust comfa 0. Comfacomsia 3dqsar of pyrimidine inhibitors of pneumocystis. Both models were validated by a test set of fifteen compounds producing very good predictive r2 values of 0.
Sastry, sushil kumar kashaw and ram kishore agrawal. Pdf how to generate reliable and predictive comfa models. The following validation techniques were used to calculate the robustness of the developed models. Chemokines are small, mainly basic proteins involved in host defense that summon. Determination of structural requirements of influenza. Comsia calculates hydrophobic, hbond donor and acceptor fields in addition to steric and electrostatic fields. The comfa and comsia models were generated using sybylx 2. Comfa, comsia, knn mfa and docking studies of 1,2,4. All the comfa and comsia models were generated via sybylx 2. To our interest, 3dqsar model suggested that the hydrophobicity of substituents was the dominating factor for the toxicities, electrostatic effect was the secondly important, and steric field gave the least contribution. Determination of structural requirements of influenza neuraminidase type a inhibitors and binding interaction analysis with the active site of ah1n1 by 3dqsar comfa and comsia modeling. The comfa model suggested that the favorable substitution of steric groups with electronegative properties at ring a.
Comfa and comparative molecular similarity indices analysis comsia methods. Structural investigations of cxcr2 receptor antagonists by comfa, comsia and flexible docking studies. Herein, 3dqsar analyses were performed on bufadienolides using comfa and comsia to learn the structureactivity relationship and the mechanism of action of these compounds. May 01, 2004 summary of comfa and comsiaresults of the training set fields opt. Pdf comfa and comsia 3d qsar models for a series of some.
The superior performance of comsia relative to comfa, with this data set, may be attributed to the higher contributions from the hydrophobic and hbd and hba fields to the comsia qsar models table 3. The noncross validated run giving the coefficient of determination r 2 values of 0. Comfa fieldbased models are constructed by calculating the value of fields, such as the electrostatic field, on a rectangular grid that encompasses the molecules in the training set. The maps generated depict regions having scaled coefficients 80% favored or file format. Comsia is insensitive to the orientation of the aligned molecules and. The similarity indices descriptors were derived with the same lattice box used in comfa. Jun 15, 2014 docking experiments on the published crystal structure of enoylacp reductase 1c14. Comfa and comsia studies on hiv1 attachment inhibitors. Unified communications and collaboration software delivering the whole stack, from traditional telephony, to voip and up to webrtc instant communication in the browser.
Comfa steric and electrostatic interaction fields were calculated at each lattice intersection on a 3d cubic lattice with grid spacing of 2 a in x, y, and z directions. Although the steric contribution was found to be the most important in both comfa and comsia, steric parameter along with electrostatic parameter produced slightly better model in comsia. Modeling study of phenylsulfonylfuroxan derivatives as p. Ars modulate a number of intracellular processes and among these. Chemokines are small, mainly basic proteins involved in host defense that summon immune cells in response to invasion by pathogenic organisms 1. Mutagen x mx exists in our drinking water as the biproducts of chlorine disinfection. Structural investigations of cxcr2 receptor antagonists by comfa, comsia and flexible docking studies shravan kumar gunda 1, rohith kumar anugolu rohit. Qsar and molecular docking of phthalazine derivatives as. The validity of developed models was assessed by test set of 9 compounds, which showed good predictive correlation coefficient for comfa 0. Research article the application of a 3dqsar approach for. Comfa, comsia, hqsar and molecular docking analysis of. The compound set was randomly divided into a training set and a test set distributed using a 23 and rule.
In comfa, the steric and electrostatic fields were calculated separately using sp3 carbon as the probe atom with the energy cutoff values of 30 kcalmol. Docking experiments on the published crystal structure of enoylacp reductase 1c14. Comparative molecular field analysis comfa and comparative. The comfa comsia models were developed using 16 compounds as training set, and externally validated using 8 compounds as test set see table 1. Relationship between the binding free energy and pcbs. Comfa, comsia, knn mfa and docking studies of 1,2,4oxadiazole derivatives as potent caspase3 activators.
Comfa, comsia, knn mfa and docking studies of 1,2,4oxadiazole derivatives as potent caspase3 activators by ankur vaidya, abhishek kumar jain, b. Comfa and comsia were employed to generate models to define the specific structural and electrostatic features essential for enhanced binding to the putative gaba receptor. Comfa, comsia, topomer comfa, hqsar, molecular docking and. Like other regression models, qsar regression models relate a set of predictor variables x to the potency of the response variable y, while classification qsar models relate the predictor variables to a categorical value. The surflexdock module of sybyl x was used for molecular docking studies.
Mx and its analogs are synthesized and modeled by quantitative structure activity relationship qsar methods. Molecular modeling studies on benzimidazole carboxamide. The statistical results of comfa and comsia models in terms of activities against k562 and sw1116 cells. Nov, 2008 a 3dqsar comfa study requires the superimposition of a set of active molecules that are kept in a 3d grid space as the steric and electrostatic fields are calculated at various grid points. Contour maps generated from comfa and comsia show regions of the molecular structure where modifications in the steric, electrostatic. Oct 15, 2006 read development of new comfa and comsia 3dqsar models for antiinflammatory phthalimidecontaining tnf. The ability of these models was validated by 16 compounds of the test set. Being one of the most potent mutagen, it attracted much attention from many researchers. This study was based on common structural alignments. Nigus dessalew and sanjeev kumar singh affiliation. If the inline pdf is not rendering correctly, you can download the pdf file here. Ligand based comfa, comsia and hqsar analysis of ccr5. All the developed models were tested for robustness using various validation techniques.
Unlike comsia, comfa does not have explicit hydrophobic and hydrogenbonding descriptors, which are assumed to be implicitly treated in the comfa. Quantitative structureactivity relationship models qsar models are regression or classification models used in the chemical and biological sciences and engineering. Apr 23, 2018 comsia comparative molecular similarity index analysis comsia is a method developed recently as an extension of comfa. Comfa and comsia 3dqsar analysis of dmdp derivatives as anticancer agents article pdf available in bioinformation 29. Genyan liu xiulian ju jin cheng zhiqiang liu issue date.
To generate statistically significant 3dqsar models. The results obtained were subjected to extensive external validation q 2, r 2, r 2 m, etc. Research article the application of a 3dqsar approach for 7. Both of the predicted and actual pic 50 values of the training and test set compounds are displayed in table 1. Furthermore, comsia model indicated the possible role of h bond donor.
Read development of new comfa and comsia 3dqsar models for antiinflammatory phthalimidecontaining tnf. Molecular docking and molecular dynamics simulations. College of medicine, chosun university, 375 seosukdong, donggu gwangju 501759, republic of korea. Unlike previous result of comfa, in our case steric parameter alone gave the best statistics. The values of leave five out, external test set r 2 pred, bootstrapping, progressive scrambling q 2 and rm 2 metric calculation for comfa and comsia models were within the suggested range.
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