BackgroundWeak intermolecular interactions such as hydrogen bonding and hydrophobic interactions are key players in stabilizing energetically-favored ligands, in an open conformational environment of protein structures. However, it is still poorly understood how the binding parameters associated with these interactions facilitate a drug-lead to recognize a specific target and improve drugs efficacy. To understand this, comprehensive analysis of hydrophobic interactions, hydrogen bonding and binding affinity have been analyzed at the interface of c-Src and c-Abl kinases and 4-amino substituted 1H-pyrazolo [3, 4-d] pyrimidine compounds.MethodologyIn-silico docking studies were performed, using Discovery Studio software modules LigandFit, CDOCKER and ZDOCK, to investigate the role of ligand binding affinity at the hydrophobic pocket of c-Src and c-Abl kinase. Hydrophobic and hydrogen bonding interactions of docked molecules were compared using LigPlot program. Furthermore, 3D-QSAR and MFA calculations were scrutinized to quantify the role of weak interactions in binding affinity and drug efficacy.ConclusionsThe in-silico method has enabled us to reveal that a multi-targeted small molecule binds with low affinity to its respective targets. But its binding affinity can be altered by integrating the conformationally favored functional groups at the active site of the ligand-target interface. Docking studies of 4-amino-substituted molecules at the bioactive cascade of the c-Src and c-Abl have concluded that 3D structural folding at the protein-ligand groove is also a hallmark for molecular recognition of multi-targeted compounds and for predicting their biological activity. The results presented here demonstrate that hydrogen bonding and optimized hydrophobic interactions both stabilize the ligands at the target site, and help alter binding affinity and drug efficacy.

[1] From the simultaneous measurements of aerosol optical, physical, and chemical characteristics over Hisar, a semiurban location in northern India, aerosol radiative (shortwave (SW), longwave (LW), and net) forcings are estimated using a radiative transfer model. The submicron aerosol mass concentrations are found to be similar, while the supermicron mass concentrations on hazy and foggy days are found to be higher than those found during clear days. Aerosol optical depths are found to be high on foggy days, and they decrease on hazy and clear days. Black carbon (BC) aerosol mass concentration is found to be low during clear and hazy periods and increases by about a factor of 5 during foggy days. Single-scattering albedo (w) values at 0.5 mm are found to be 0.88, 0.86, and 0.76 for clear, hazy, and foggy conditions, quite in agreement with varying BC amounts. The w values over Hisar are found to exhibit close correspondence with w derived from other locations in India in winter. SW atmospheric (ATM) forcing is found to increase from 16 W m À2 during clear periods to 49 W m À2 for foggy days. LW cooling of the ATM increases from about À2 W m À2 for clear conditions to about À3 W m À2 during foggy periods. LW ATM forcings are found to contribute 11-14% to the net ATM forcing. As the LW ATM forcings are negative, they partially cancel the large SW ATM warmings. Sensitivity study shows that LW ATM cooling becomes more prominent with an increase in the amount of absorbing aerosols and decrease in water vapor, while LW forcings are found to vary only by 1% for differing ozone amounts.

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Abstract.A detailed study on the changes in aerosol physical and optical properties during fog events were made in December 2004 at Hissar (29.13 • N, 75.70 • E), a city located in the Indo-Gangetic basin. The visible aerosol optical depth was relatively low (0.3) during the initial days, which, however, increased (0.86) as the month progressed. The increasing aerosol amount, the decreasing surface temperature and a higher relative humidity condition were found favoring the formation of fog. The fog event is also found to alter the aerosol size distribution. An increase in the number concentration of the nucleation mode (radius<0.1 µm) particles, along with a decrease in the mode radius showed the formation of freshly nucleated aerosols. In the case of accumulation mode (0.1 µm

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The solid-state structure of an alkaline-earth metal complex reveals the formation of a remarkable supramolecular framework based on concurrent lone pair-pi, pi-pi, and pi-anion interactions whose stability has been investigated by density functional theory.

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In this paper, we study on the precursor seed structures well before the prospective occurrence of equatorial plasma bubble (EPB). We use the scanning mode observations made by the 30‐MHz Gadanki Ionospheric Radar Interferometer for estimating interbubble spacing and high time resolution observations made by a collocated digisonde for inferring horizontal wavelength of wave‐like variations prior to the onset of EPB. Horizontal wavelength of wave‐like variations has been inferred from plasma density variations and height variations of isodensity contours; both show consistent results. Remarkable agreement has been found between the estimated horizontal wavelength and interbubble spacing, which demonstrates the potential of digisonde in providing relevant seed structure for a prospective EPB formation. Further analysis based on observational results and numerical simulation of collisional interchange instability shows that while the eventual formation of EPB has a strong bearing on the height of the F layer and density gradient scale length, the growth perspective of the EPB depends on the seed wavelength. These results are presented and discussed keeping the future prospective of EPB forecasting/nowcasting.