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Preliminary Phytochemical Screening and Identification of Bioactive Compounds from Banana Inflorescence and to Find the Interactions on Molecular Docking for PCOS
Published in Parimelazhagan Thangaraj, Phytomedicine, 2020
M. C. Kamaraj, Suman Thamburaj, R. Akshaya, V. Bhanu Deepthi
The protein sequence was subjected for comparative homology modeling via Swiss-model (Kiefer et al. 2008) and evaluated by the RAMPAGE online server (Lovell et al. 2003). The protein was validated by using the online server PROCHECK (Laskowski et al. 1996). The Swiss-model performs the sequence alignments and searches for the putative template protein for generating the 3D model.
Carboxylesterase Inhibitors: Relevance for Pharmaceutical Applications
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
The three-dimensional structures of several mammalian CES, including human carboxylesterase 1 (CES1), have been solved by X-ray crystallography with several ligands (Potter et al., 1998; Bencharit et al., 2002; Bencharit et al., 2003a; Bencharit et al., 2003b; Furihata et al., 2004; Fleming et al., 2007). As depicted in Fig. 9.1, CES1 is composed by a central catalytic domain, an αβ domain, and an adjacent regulatory domain which containing the low-affinity surface ligand-binding Z-site. The X-ray crystal structure of CES1 demonstrated its existence as monomer, trimer, or hexamer, with substrate dependent equilibrium of homooligomer formation. In contrast, CES2 exist as monomers. Both sequence alignments and secondary sequence predictions have suggested that these three CES are members of α/β hydrolase family (Holmes et al., 2009). Although the three-dimensional structures of CES2 have not been reported, the 3D structure modeling of CES2 could be downloaded from the SWISS-MODEL repository (a database of annotated 3D protein structure models generated by the SWISS-MODEL homology-modeling pipeline).
Innovations in medical education
Published in Caragh Brosnan, Bryan S. Turner, Handbook of the Sociology of Medical Education, 2009
A third problem is that at the labour market end there seems to be no real need for a Bachelor in medicine. At first glance, a Bachelor in medicine does not make much sense, though the EU countries of Portugal, the Netherlands and Denmark have adopted a two- tier system of 3+3 years, compliant with the mandate in Europe to have a six- year medicine curriculum. In Belgium (3+4 years) a Bachelor degree in medicine also exists, but this does not qualify the candidate for the labour market. Swiss medical faculties, however, have taken an alternative route in developing a flexible curriculum with a labour-market-relevant Bachelor degree, different Master’s tracks and research opportunities. The Swiss model allows students to choose between different major and Master’s programmes and to diversify in tracks such as research and medical practice (Probst et al. 2007). Because the Swiss model no longer results in one single type of graduate, paths to other professions in the healthcare area are opened up. Though the Swiss model looks promising, many countries are further from putting into practice the Bologna principles in medical education.
The discovery and development of transmembrane serine protease 2 (TMPRSS2) inhibitors as candidate drugs for the treatment of COVID-19
Published in Expert Opinion on Drug Discovery, 2022
Christiana Mantzourani, Sofia Vasilakaki, Velisaria-Eleni Gerogianni, George Kokotos
Pooja et al. used the PSI-BLAST tool to search for high homology proteins in RCSB PDB. SWISS-MODEL server was used for building the model, which was further evaluated with a number of tools [104]. HADDOCK, CLUSPRO, and dog site server used to determine the binding site in order to dock seven marketed drugs and eighteen natural compounds with Autodock VINA in TMPRSS2. The S1 domain was identified to consist of the following amino acids: His296, Ser441, Asp345, Gly496, Gln438, Gln498, Gln506, Tyr505 and His296, Ser441, Asp345, Asn437 Gly404, Asp405, Gly496 and Gln498. For the evaluation of the docking results, camostat was used as the reference compound. Based on their docking results, camostat forms hydrogen bonds with His296, Cys281, Glu389, Lys390 and Gln438, while the formation of van der Waals interactions with Trp461, Gly462, Ser460, Gly385, His279, Thr393, Lys392 and Gly391 help to stabilize the complex. The authors also mention the carbon–hydrogen interactions with the catalytic Ser441 and Gly439, Cys297 and Leu302. Meloxicam, nafamostat, ganodermanontriol, columbin, myricetin, proanthocyanidin A2, jatrorrhizine and baicalein were the compounds with the highest docking scores. For nafamostat, the authors described its van der Waals interactions with the catalytic Ser441 and His296 and the formation of three hydrogen bonds with Ser436, Asp435 and Gly461. Interestingly, based on their docking results, meloxicam forms three hydrogen bonds with Gly462, Ser441, and Ser460, while several van der Waals interactions stabilize the complex.
Development linear and non-linear QSAR models for predicting AXL kinase inhibitory activity of N-[4-(quinolin-4-yloxy)phenyl]benzenesulfonamides
Published in Journal of Receptors and Signal Transduction, 2019
Roya Ahmadi, Bakhtyar Sepehri, Raouf Ghavami
All calculations were run on a 2.5GHz Intel® CoreTM2 Quad Q 8300 CPU with 4 GB of RAM using all four available cores under Windows 7 (64-bit) operating system. The building of three-dimensional structures of molecules and their optimization were done by using HyperChem (version 7.1, HyperCube, Inc.) [29]. OpenBabel software (version 2.3.2) [30] was used to convert molecular format files. Open3DALIGN software (version 2.27) [31,32] and Open3DQSAR software (version 2.282) [33,34] were used to perform alignment analysis and build CoMFA models, respectively. PyMOL software (version 1.7.0.0) [35] was used to visualize the results of alignment analysis and counter maps of CoMFA models. Dragon software (version 5.5) [36] was used to calculate descriptors. Discovery Studio visualizer software (version 16.1.0) [37] was used to create two-dimensional interactions between ligands and Axl. Universal Protein Resource (UniProt) web platform was used to take the amino acids sequence of Axl receptor [38,39]. SWISS-MODEL web platform was used to create the homology model of Axl protein structure [40–42]. SwissDock web platform was used to dock molecules to Axl structure [43,44]. Least squares support vector machine analysis was performed by LS-SVMlab toolbox in Matlab software (version R2010a) [45]. ANN toolbox in Matlab software (version R2010a) was used to create a feed-forward neural network with back propagation training algorithm [46]. SPSS software (version 16.0, SPSS, Inc.) was used for elimination selection stepwise MLR analysis [47].
Investigating protein–excipient interactions of a multivalent VHH therapeutic protein using NMR spectroscopy
Published in mAbs, 2022
Jainik Panchal, Bradley T. Falk, Valentyn Antochshuk, Mark A. McCoy
Interaction profiling was accomplished using a protein-enhanced diffusion-ordered spectroscopy (DOSY) experiment, Figure 4a. First, we collected translational self-diffusion data on the MV-VHH with 0% sucrose. The detection dimension of this data set is dominated by protein peaks, but an acetate signal was also identified at 1.9 ppm. From the MV-VHH diffusion data, a hydrodynamic radius, Rh, of 3.7 nm was calculated, whereas the aC and aD fragments had a hydrodynamic radius of 1.65 nm. These data indicate that the MV-VHH is in an extended conformation, which is consistent with the 2D 1H,13C sfHMQC fingerprinting studies in Figure 2, which found that the folded VHH domains are flexibly linked with minimal intramolecular interactions. The cartoon in Figure 4b is a PyMOL27 model of the MV-VHH protein that incorporates NMR Rh determination, with non-interacting domain positioning. The protein structure is a homology model, created using the SWISS-model,28 using the MV-VHH primary sequence. Rh was calculated with HullRad.29 The aC VHHs are shown in orange, and the aD VHH is shown in green. The VHHs are joined by a flexible 35-residue linker shown in gray. The gray sphere (radius 2.8 nm) represents the extent of the surface anticipated from a compactly folded, single domain 42 kDa protein. Note that while our model for the MV-VHH protein is not compact, it is not completely extended, with a minimum interdomain distance ~30 Å