TIFR
Department of Chemical Sciences
School of Natural Sciences

Calender

August 9, 2016 at 4.00 pm in AG-80

Title :

Structural and Functional Characterization of an Unusual Ca2+ Binding Protein from E. histolytica

May 9, 2016 at 4.00 pm in AG-69

Title :

Understanding the Role of Specific Hydrophobic Interaction in Amyloid Conformation and Function

 

May 6, 2016 at 2.30 pm in AG-80

Title :

Biophysical Insights into the Ras-Membrane Interactions

Abstract :

This talk would deal with the biophysical study of Ras protein-membrane interactions. Ras proteins existing as four isoforms, act as membrane-associated molecular switches in the early steps of signal transduction pathways associated with cell growth and differentiation. For their biological activity, these proteins need to be anchored to membranes, which is achieved by post-translational lipidation. Deregulated isoform-specific Ras signaling accounts for 30% of all human tumors, thus placing them at the focal point of academic and pharmaceutical research. Despite their enormous potential as drug targets, pharmacological intervention of Ras driven cancers has not been realized till date and is dubbed as a “holy grail” in cancer therapy. Due to the common structures of Ras isoforms, most drugs often lead to undesirable off-target effects. Thus, a major hurdle in drugging Ras in a specific manner has been the lack of detailed molecular level characterization of these proteins in their cellular environments. Using various state-of-the-art spectroscopic and microscopic techniques,comprehensive biophysical characterization of the structural and conformational changes in Ras isoforms, upon incorporation into heterogeneous model membrane systems, was accomplished. The main results elucidate key codecs for Ras isoform diversity, providing critical hints to target Ras in an isoform-specific manner. Moreover, highly decisive and critical roles for lipid membranes in Ras protein biophysics, ranging from dictating Ras orientational flexibility, conformational dynamics, and mechanosensitivity, to modulating the interactions of Ras with other proteins would be demonstrated by the presented work.

May 5, 2016 at 2.30 pm in AG-80

Title :

Small-molecule Mediated Modulation of Signaling Pathways

Abstract :

The talk will focus on small molecule–mediated modulation of signaling pathways. Systematic application of small molecule modulators of protein function for the study of biological networks involved in signaling pathways lies at the heart of an experimental approach termed as Chemical Biology.

Wnt signaling is a branch of a functional network involved in a broad range of biological processes, such as development and homeostasis. It is one of the fundamental oncogenic pathways, and is implicated in multiple cancers. Thus targeting this pathway is an attractive therapeutic approach. Within the framework of biology oriented synthesis (BIOS), screening of the natural product inspired withanolide-based compound collection revealed potent inhibitors of Wnt signaling (IC50 = 100 nM) in human colorectal cancer cells. An assortment of different biochemical, cell biological and proteomic methods-based primary and secondary assays, were used to validate the bioactivity of our „lead compound“ in the Wnt pathway. Our efforts towards identification of the compound’s target protein will be discussed. Through a similar approach in a parallel project, a potent and selective small molecule inhibitor of cytokinesis was identified and validated.

 

May 2, 2016 at 4.00 pm in AG-69

Title :


Fluorescent Sensors for Imaging the Signal Mediating Phospholipids

April 25, 2016 at 4.00 pm in AG-69

Title :

Understanding the Mechanical Properties of Azurin Using Single Molecule Force Spectroscopy and Steered Molecular Dynamics

April 21, 2016 at 2.30 pm in AG-80

Title :

Novel Protein Targets of Multi Drug Resistant Acinetobacter baumannii

Abstract :

In the current scenario, widespread multidrug resistivity in ESKAPE pathogens demands identification of novel drug targets to keep their infections at bay. For this purpose, we have identified histone acetyltransferase Hpa2 and DNA-repair enzyme TAG of A. baumannii. Correct sequence alignment and construction of 3D monomeric and dimeric models of proteins having optimal structural parameters is a troublesome task. To overcome these problems, we have designed an easy and optimized protocol for homology modeling. Improvement in the structural features of protein is an onerous process and generally achieved by paying time and computational cost. Herein, it is achieved by reconciliation of FoldX commands which takes less time in execution. Evaluations performed to validate structural parameters and stability of models attests to its quality.

Hpa2 and TAG protein genes were cloned and heterologously expressed in bacterial expression system. The expressed protein was purified up to 98% homogeneity by a two-step purification protocol involving affinity purification followed by the size exclusion chromatography step. The biophysical studies (CD, Fluorescence and ITC) were carried out to characterize the structural and substrate/inhibitors binding parameters.The oligomeric state of enzymes determined in presence of various substrates as well as in extreme physiological conditions using analytical size exclusion, native PAGE and glutaraldehyde crosslinking assay. The enzyme activity is checked using simplified HPLC based biochemical assay. The Hpa2 and TAG proteins were put onto crystallization trials using commercial Hampton screens. The outcomes of these studies will be presented.  

April 18, 2016 at 4.00 pm in AG-69

Title :

Design of CO2 Sorbents Using Functionalized Fibrous Nanosilica (KCC-1: Insights into the Effect of the Silica Morphology (KCC-1 vs. MCM-41)

April 11, 2016 at 4.00 pm in AG-69

Title :

TiO2 coated fibrous nanosilica (KCC-1) for photocatalysis: Particle formation and size quantization

April 4, 2016 at 4.00 pm in AG-69

Title :

Visible Light Triggered Organic Photochemistry inside Water-soluble Nanocages

March 28, 2016 at 4.00 pm in AG-69

Title :

Designer ligands for Mn2+  selective chelation and detection

February 29, 2016 at 4.00 pm in AG-69

Title :

Computational Studies of Optical Charge Transfer Transitions in Non-aromatic Amino Acids and Metal-ligand Complex

February 26, 2016 at 2.30 pm in AG-80

Title :

Directed Evolution of Cytochrome P450 : An Approach to Engineer Thermally Stable Enzyme

February 25, 2016 at 2.30 pm in AG-80

Title :

Elephant, Blind Man, Molecule - Surface Scattering and Surface Chemistry

Abstract :

Understanding the mechanism of energy transfer from a molecule to a metal surface is essential for  building an atomic/molecular level description of surface chemistry. In this talk I will describe some general ideas regarding how a molecule exchanges translational, rotational and vibrational energy when it interacts with a metal surface. I will discuss this in the context of some of our recent work based on quantum state resolved inelastic scattering experiments of diatomic molecules such as: CO, NO and HCl scattering from Au(111) surface.

Further, I will also talk about the process of dissociation of a molecule on a metal surface using  some of our recent work on the HCl/Au(111) system as an example. Our study of this process points towards serious limitations in the the currently available state of the art theoretical methods.  These methods, based on 6-D quantum dynamical simulations using density functional theory based potential energy surface, relying on the Born-Oppenheimer and the rigid surface approximation which have worked well in describing previously well studied dissociation process such as H2 on Cu(111) and N2 on Ru(0001), severely overestimate the dissociation probability when compared to our experiments.

February 22, 2016 at 2.30 pm in AG-66

Title :

Temperature Dependent Protein Malleability (stiffness) Probed by Force and Fluorescence