biomodeling talk on Thursday by Indira Ghosh
Chetan Gadgil
Dear colleagues,
All are invited for a talk by Prof. Indira Ghosh
Title: Protein Structure & Function: Novel Revelations.
Affiliation: TeOra (teoralife.com); previously: School of Computational and Integrative Sciences, JNU; Bioinformatics center, SPPU
Time: 4th September, Thursday 03:00 - 4:30pm
Venue: CEPD lecture Hall, CSIR-NCL
There will be time for an informal interaction with the speaker over tea
after the talk.
About the speaker: Prof. Indira Ghosh, a pioneer in bioinformatics, has significantly shaped computational biology in India. She founded JNU's School of Computational and Integrative Sciences, spearheaded initiatives in complex systems and bioinformatics education, initiated the DBT BINCE program for bioinformatics PhD program and contributed to groundbreaking research in drug discovery through various projects at SPPU, JNU and at AstraZeneca.
Abstract:
With the knowledge of too many protein structures in deeper detail, it’s reasonable to consider that protein structures are well characterized and projected as very compact in nature but functionally highly flexible. “How has this happened?” is my question since long. Many answers are available, like Dynamics of protein structure, many different folding with smallest change in sequence, limited secondary structures, thermodynamics of stable protein etc. As the prediction from sequence to structure is reaching a new height, thanks to AI tools, we are intrigued to learn more at the local events in protein structures, like modularity & compactness. Modularity played an important role in simplifying protein structure in three dimensions. Identification of the smallest component of protein’s modular structural arrangement will provide an insight into its evolution and structural–functional space. But in case of protein structure context, defining “module” becomes a challenging problem (Banerji & Ghosh, 2011& Rorick, 2012). An attempt has been made to provide a systematic approach to identify structural modules using component-based approach by considering the arrangement of secondary structural elements (SSEs), strict geometrical sense. For concise representation of contact among SSEs in proteins, “contact string” has been developed, like “fingerprints”. Given a set of SSEs, “contact string” can uniquely represent all different contact patterns, which unravel all possible structures, however it’s interesting to observe that functional proteins are very choosy, only few of them occur. Our group has developed ProLego, an application to explore the component aspect of protein structures and provide an intuitive and efficient way to scan the protein topology space. One interesting observation was that the set of topologies that are found to be structurally prevalent are functionally divergent (Khan & Ghosh, 2015 & Khan, Panday & Ghosh, 2018 ). Regarding compactness measurement of protein has been attempted by many geometrical and biophysical parameters and related with the nature of folding of the soluble proteins. However, classical measures like radius of gyration, density of protein & Hydrophobicity of protein are not able to explain the ‘complex systems’ like protein and its biophysical properties like innate mesoscopic nature, inhomogeneous and ‘self organized criticality’ which are nonlinear behaviors. Fractal dimension (FD) can be calculated for objects who are described by non-integer dimensions and who have self-similarity. In our group, fractal dimension measure (geometric or statistical) for proteins have been used to detect the invariant patterns in variables of innately inhomogeneous nature; namely mass, hydrophobicity and polarizability distributions in protein interior and measures them with respective FD values which are unambiguous, single-valued, objective markers. Using such measures, it was found that irrespective of the classification, all the globular proteins have some untapped Hydrophobicity, greater in thermophilic than mesophilic proteins. The results can be utilized in designing proteins to strike a balance with their marginal structural stability and the folding constrains like their intrinsically small secondary structural units (alpha helix & beta sheet). (Banerji & Ghosh ,2009 & 2013) Hence, the proper representation and local structural defects may have reasons to keep proteins alive i.e., compact but functionally flexible!
Banerji, A., & Ghosh, I. (2011) Fractal symmetry of protein interior: What have we learned? Cellular and Molecular Life Sciences, 68, 2711–2737. Rorick, M. M. (2012. Quantifying protein modularity and evolvability: A comparison of different techniques. Biosystems,110, 22–33. Khan T, Ghosh I. (2015) Modularity in protein structures: study on all-alpha proteins. J Biomol Struct Dyn.;33:2667–81. Taushif Khan, Shailesh Kumar Panday and Indira Ghosh. (2018) ProLego: tool for extracting and visualizing topological modules in protein structures. BMC Bioinformatics (2018) 19:167. Banerji A, Ghosh I (2009) Revisiting the Myths of Protein Interior: Studying Proteins with Mass-Fractal Hydrophobicity-Fractal and Polarizability-Fractal doi:10.1371/journal.pone.0007361 Dimensions. PLoS ONE 4(10): e7361. Banerji A, Ghosh I (2013) Effectiveness of Fractal Dimension based Measures to Investigate Protein structures. In Biomolecular Forms & Functions, A celebration of 50 Years of the Ramachandran Map. Ed. Manju Bansal & N. Srinivasan, Publishers IISc Press-WSPC Publication. page 482-491.
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Chetan Gadgil, PhD
Scientist, Chemical Engineering Division,
National Chemical Laboratory, Pune 411008
Dean, Engineering Sciences, AcSIR
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