The molecular principles of N-end rule recognition

Sriram, Shashikanth M,Kwon, Yong Tae Nature Publishing Group, a division of Macmillan P 2010 Nature Structural and Molecular Biology Vol.17 No.10

Development and Characterization of Monomeric N-End Rule Inhibitors through <i>In Vitro</i> Model Substrates

Sriram, Shashi,Lee, Jung Hoon,Mai, Binh Khanh,Jiang, Yanxialei,Kim, Yongho,Yoo, Young Dong,Banerjee, Rajkumar,Lee, Seung-Han,Lee, Min Jae American Chemical Society 2013 Journal of medicinal chemistry Vol.56 No.6

<P>In the N-end rule pathway, a set of N-terminal amino acids, called N-degrons, are recognized and ubiquitinated by the UBR proteins. Here we examined various N-end rule inhibitors to identify essential structural components of the system. Our study using <I>in vitro</I> biochemical assay indicated that the <SMALL>l</SMALL>-conformation and protonated α-amino group of the first residue were critical for N-degrons to properly interact with the UBR proteins. The monomeric molecules with minimum interacting motifs showed endopeptidase resistance and better inhibitory activities than traditional dipeptide inhibitors. Collectively, our study identifies a pharmacophore of N-end rule inhibitors, which provides a structural platform to improve the efficiency and druggable properties of inhibitors. Considering that the N-end rule has been implicated in many pathophysiological processes in cells, inhibitors of this pathway, such as <I>p</I>-chloroamphetamine, are potentially of clinical interest in a novel aspect of action mechanisms.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/2013/jmcmar.2013.56.issue-6/jm400046q/production/images/medium/jm-2013-00046q_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jm400046q'>ACS Electronic Supporting Info</A></P>

2P-365 Blind/Focussed Docking Studies on Ligand Binding Mode to Lipocalin Proteins

( Sriram Sokalingam ),이선구 한국공업화학회 2017 한국공업화학회 연구논문 초록집 Vol.2017 No.1

Lipocalins are diverse group of proteins with varied functions, such as transport, pheromone activity, camouflage, immunomodulation, olfaction, enzymatic synthesis and regulation of cell homeostasis. Therefore, understanding the ligand binding modes of these distinctive functional lipocalins will render a clear understanding about the dynamicity of lipocalins for scaffold protein engineering. In this study, we characterized the binding modes of various ligands to lipocalin protein by performing docking studies. Specifically, blind dockings were attempted to understand the specific and nonspecific bindings of ligands, and focussed docking study was carried out to characterize the specific binding of ligands.

Deciphering the Factors Responsible for the Stability of a GFP Variant Resistant to Alkaline pH Using Molecular Dynamics Simulations

Sriram Sokalingam,Bharat Madan,Govindan Raghunathan,이선구 한국생물공학회 2013 Biotechnology and Bioprocess Engineering Vol.18 No.5

Charged amino acids having ionizable side chains play crucial roles in maintaining the solubility and stability of a protein. These charged amino acids are mostly exposed on protein surface and participate in electrostatic interactions with neighboring charged amino acids as well as with solvent. Therefore, the change in the solvent pH affects the protein stability in most cases. Previously, we reported a GFP variant, GFP14R having 14 surface lysines replaced with arginines, that showed enhanced stability under alkaline pH. Here, we analyzed the factors that contribute to the stability of the GFP14R under alkaline pH quantitatively using molecular dynamics simulations. Protonation state of the charged amino acids of GFP14R and control GFP under neutral pH and alkaline pH were modeled,and molecular dynamics simulations were performed. This comparative analysis revealed that the GFP14R with more arginine frequency on the surface maintained the stability under both pH conditions without much change in their salt-bridge interactions as well as the hydrogen bond interactions with solvent. On the other hand, these interactions were significantly reduced for the control GFP under alkaline pH due to the deprotonated lysine side chains. These results suggest that the advantageous property of arginine over lysine can be considered one of the parameter for the protein stability engineering under alkaline pH conditions.

In silico Study on the Effect of Surface Lysines and Arginines on the Electrostatic Interactions and Protein Stability

Sriram Sokalingam,Bharat Madan,Govindan Raghunathan,이선구 한국생물공학회 2013 Biotechnology and Bioprocess Engineering Vol.18 No.1

Charged amino acids are mostly exposed on a protein surface, thereby forming a network of interactions with the surrounding amino acids as well as with water. In particular, positively charged arginine and lysine have different side chain geometries and provide a different number of potential electrostatic interactions. This study reports a comparative analysis of the difference in the number of two representative electrostatic interactions,such as salt-bridges and hydrogen bonds, contributed by surface arginine and lysine, as well as their effect on protein stability using molecular modeling and dynamics simulation techniques. Two in silico variants, the R variant with all arginines and the K variant with all lysines on the protein surface, were modeled by mutating all the surface lysines to arginines and the surface arginines to lysines,respectively, for each of the 10 model proteins. A structural comparison of the respective two variants showed that the majority of R variants possessed more salt-bridges and hydrogen bond interactions than the K variants, indicating that arginine provides a higher probability of electrostatic interactions than lysine owing to its side chain geometry. Molecular dynamics simulations of these variants revealed the R variants to be more stable than the K variants at room temperature but this effect was not prominent under protein denaturating conditions, such as 353 and 333 K with 8 M urea. These results suggest that the arginine residues on a protein surface contribute to the protein stability slightly more than lysine by enhancing the electrostatic interactions.

A Study of the<i>Kepler K2</i>Variable EPIC 211957146 Exhibiting a Variable O’ Connell Effect

Sriram, K.,Malu, S.,Choi, C. S.,Rao, P. Vivekananda American Astronomical Society 2017 The Astronomical journal Vol.153 No.5

<P>We present the multi-band photometric and spectroscopic study of an over-contact binary system, EPIC 211957146. The light curves exhibit a variable O' Connell effect, confirmed from our observational data and the Kepler K2 data. The best photometric solution incorporating a dark spot over the primary component unveils that the system has a low-mass ratio (q similar to 0.17) and a high inclination (i similar to 85 degrees). To confirm the solution and constrain the uncertainty, Monte-Carlo simulations are performed and the results are reported. Based on the O-C diagram analysis, we see that the variable shows a period increase at the rate of dP/dt similar to 1.06. x. 10(-6) days yr(-1), which is higher than the theoretically predicted value. Presence of a third body having a period of similar to 16.23 years is evident from the O-C diagram. No filled-in effect is observed in the Ha line, while the effect is vividly present in the Na line. From the Kepler K2 data, we found that the primary and secondary minima exhibit an anti-correlated O-C variation followed by an erratic behavior. This is possibly caused by the longitudinal motion of the spot, and hence, we set a lower limit of similar to 40 days for the spot modulation. We also observe a possibly associated photometric difference in the primary depth by comparing our light curves with Kepler K2 normalized light curves. This system has a low-mass ratio and a high fill-out factor, and, theoretically, such a physical configuration would lead to a merger.</P>

A detection of an anti-correlated hard X-ray lag in AM Herculis

Sriram, K.,Choi, C. S.,Rao, A. R. EDP Sciences 2011 Astronomy and astrophysics Vol.525 No.-

Structure-Property relationship of Nylon/Clay Nanocomposites

Sriram Venkataramani,박민규,김성철 한국고분자학회 2004 한국고분자학회 학술대회 연구논문 초록집 Vol.29 No.2

Amine activated diatom xerogel hybrid material for efficient removal of hazardous dye

Sriram, Ganesan,Bhat, Mahesh P.,Kigga, Madhuprasad,Uthappa, U.T.,Jung, Ho-Young,Kumeria, Tushar,Kurkuri, Mahaveer D. Elsevier 2019 Materials chemistry and physics Vol.235 No.-

<P><B>Abstract</B></P> <P>The effective removal of organic pollutants from aqueous media is still an eminent challenge. In the present work, naturally available diatomaceous earth (DE) particles was surface modified with mesoporous silica xerogel denotes as diatom xerogel material. Subsequently amine functionality has been successfully introduced on diatom xerogel (DXEA) for the efficient removal of hazardous dye, Eriochrome Black T (EBT). The adsorbents before and after EBT adsorption were characterized using various techniques such as XRD, FE-SEM, FTIR and BET. The adsorption process was conducted by varying many parameters such as pH, dosage, initial concentration of dye and time. The designed adsorbent, DXEA showed increased removal efficiency (∼99 %) in comparison with neat DE (∼58 %) due to the presence of amine functional group, which favours the rapid adsorption of EBT. This study showed that adsorbent DXEA was adequate to remove 50 mg/L and 100 mg/L of aqueous EBT in 5 and 60 min of contact time respectively. The maximum dye adsorption capacity of DXEA was found to be ∼62 mg/g whereas, for DE it was ∼56 mg/g. The dye adsorption kinetics of EBT onto both the DXEA and the DE follow the pseudo-second-order model. Also, DXEA was used for selective removal of EBT in the presence of other dyes and recycle studies were discussed. These studies showed that DXEA is a promising material for EBT removal by adsorption in real sample.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Amine activated diatom xerogel adsorbent was synthesized for efficient removal of EBT. </LI> <LI> Adsorbent was analyzed using XRD, FESEM, FTIR and BET before and after dye adsorption. </LI> <LI> The designed adsorbent showed 99.9% EBT removal efficiency within 5 min. </LI> <LI> Selective removal of EBT was observed over other cationic and anionic dyes. </LI> <LI> The amine activated diatom xerogel showed good reusability even after five cycles. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Validation on the molecular docking efficiency of lipocalin family of proteins

Sriram Sokalingam,Ganapathiraman Munussami,김중래,이선구 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.67 No.-

Lipocalins are diverse group of small extracellular proteins found in various organisms. In this study, members of 10 non-homologous lipocalin–ligand crystal complex structures were remodeled using rigid and flexible ligand modes to validate the prediction efficiency of molecular docking simulation. The modeled ligand conformations indicated a high prediction accuracy in rigid ligand mode using cluster based analysis for most cases whereas the flexible ligand mode required further considerations such as ligand binding energy and RMSD for some cases. This in silico study is expected to serve as a platform in the screening of novel ligands against lipocalin family of proteins.