Protein-Protein Docking With F2Dock 2.0 and GB-Rerank.

Protein-Protein Docking with F2Dock 2.0 and GB-Rerank.

PLoS One. 2013; 8(3): e51307
Chowdhury R, Rasheed M, Keidel D, Moussalem M, Olson A, Sanner M, Bajaj C

Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F2 Dock protocol which improves the state of the art in initial stage rigid body exhaustive docking search, scoring and ranking by introducing improvements in the shape-complementarity and electrostatics affinity functions, a new knowledge-based interface propensity term with FFT formulation, a set of novel knowledge-based filters and finally a solvation energy (GBSA) based reranking technique. Our algorithms are based on highly efficient data structures including the dynamic packing grids and octrees which significantly speed up the computations and also provide guaranteed bounds on approximation error.The improved affinity functions show superior performance compared to their traditional counterparts in finding correct docking poses at higher ranks. We found that the new filters and the GBSA based reranking individually and in combination significantly improve the accuracy of docking predictions with only minor increase in computation time. We compared F2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F2 Dock 2.0 finds a near-native solution as the top prediction for 22 complexes; where ZDock 3.0.2 does so for 13 complexes. F2 Dock 2.0 finds a near-native solution within the top 1000 predictions for 106 complexes as opposed to 104 complexes for ZDock 3.0.2. However, there are 17 and 15 complexes where F2 Dock 2.0 finds a solution but ZDock 3.0.2 does not and vice versa; which indicates that the two docking protocols can also complement each other.The docking protocol has been implemented as a server with a graphical client (TexMol) which allows the user to manage multiple docking jobs, and visualize the docked poses and interfaces. Both the server and client are available for download. Server: Client: HubMed – drug


Allium sativum L.: the anti-immature leech (Limnatis nilotica) activity compared to Niclosomide.

Comp Clin Path. 2013 Mar; 22(2): 165-168
Bahmani M, Abbasi J, Mohsenzadegan A, Sadeghian S, Ahangaran MG

This study was carried out to determine the effects of methanolic extracts of Allium sativum L. on Limnatis nilotica compared with Niclosomide. In this experimental study in September 2010, a number of leeches (70 in total) from the southern area of Ilam province were prepared, and the effects of methanolic extract of A. sativum L. with Niclosomide as the control drug were compared and distilled water was evaluated as the placebo group which investigated L. nilotica using anti-leech assay. The average time of paralysis and death of L. nilotica for Niclosomide (1,250 mg/kg) and the methanol extract of A. sativum L. (600 ?g/ml) were 6.22?±?2.94 and 68.44?±?28.39 min, respectively. Distilled water and garlic tablets at a dose of 400 mg were determined as the inert group. In this research, the attraction time of the leeches’ death among different treatments is significant. In this study, it was determined that Niclosomide, with an intensity of 4+, and methanolic extracts of A. sativum L., with an intensity of 3+, have a good anti-leech effect and can be shown to be effective in cases of leech biting, while distilled water was negative. HubMed – drug


Optimization of mobile phase for the determination of Esomeprazole and related compounds and investigation of stress degradation by LC-MS.

J Sep Sci. 2013 Jan 24;
Dong Q, Zhu J, Sui Q, Tang C, Wang X, Yu Y

In this study, the objective was to investigate the degradation behavior of Esomeprazole under different recommended stress conditions according to International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use [1] by HPLC. Our research showed that the effect of mobile phase species on separation was significant for the determination of Esomeprazole and its related compounds. Successful separation of the drug from its related impurities and degradation products formed under different stress conditions was achieved using ammonium acetate buffer/ACN by a gradient elution. Compared with phosphate buffer/ACN, ammonium acetate buffer/ACN under same pH and gradient showed a great improvement in resolution due to the change of elution order. The drug was subjected to stress conditions including acidic, alkaline, oxidative, photolytic, and thermal conditions. Extensive degradation occurred in acidic and oxidative conditions, while mild degradation was observed in alkaline and photolytic conditions. Besides, it turned out the drug was extremely stable under thermal condition. The stability-indicating LC-UV method was validated with respect to linearity, precision, accuracy, specificity, and robustness. The LC-MS method was also adopted for the characterization of degradation products. Based on the m/z values and fragmentation patterns, the degradation pathway of the drug has been proposed. HubMed – drug