Shashi Kumar
@ivanov-group.org
Postdoctorlal Research Associate
Georgia State University Atlanta
RESEARCH, TEACHING, or OTHER INTERESTS
Chemical Engineering, Biochemistry, Artificial Intelligence, Multidisciplinary
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Shashi Kumar, Vinay Kumar Duggineni, Vibhuti Singhania, Swayam Prabha Misra, and Parag A. Deshpande
Wiley
AbstractAnalysis of protein thermostability is vital in protein science to aid the understanding of evolutionary aspects of organic life as well as in protein engineering for modern day industrial applications. In the present study, supervised machine learning (ML) algorithms are employed to unravel potential patterns behind protein thermostability. This computational analysis conclusively shows inverse gamma turns, VIII turns, and the propensity of cysteine (Cys) to be the most important biophysical–biochemical attributes responsible for protein thermostability. From the propensity analysis of amino acids, polar residues, specifically glutamine (Gln) and serine (Ser), and charged residues, specifically glutamic acid (Glu) and lysine (Lys), are found to favor the enhancement of protein thermostability. The study demonstrates the feasibility of assigning quantifiable descriptors of thermostability which is expected to aid protein engineering.
Shashi Kumar, Soumya Biswas, and Parag A. Deshpande
Informa UK Limited
Abstract Maintaining the protein stability upon mutation is a challenging task in protein engineering. In the present computational study, we induced a single point Gly100Ala mutation in SazCA and examined the factors governing the stability and flexibility of the mutated form, and compared it to that of the wildtype using molecular dynamics simulations. We observed higher structural stability and lesser residual mobility in the mutated SazCA. Improved H-bonding due to Gly100Ala was observed. Ala100 was responsible for the increased helical contents in the mutated SazCA while Gly100 compromised the secondary structure contents in the wildtype. A strong network of salt bridges and high local ordering of the solvent molecules at the protein surface contributed to the enhanced stability of the mutated protein. Our simulations conclusively highlight Gly100Ala mutation as a step towards designing a more robust and thermostable SazCA. Communicated by Ramaswamy H. Sarma
Shashi Kumar and Parag A. Deshpande
Informa UK Limited
Abstract The fastest member of the carbonic anhydrase family catalysing the reversible hydration of carbon dioxide to bicarbonate ions has been recently reported to be SazCA. While thermostable, this enzyme shows exceptional activity at 353 K for the reaction. This study explores the molecular basis for the exceptional activity of SazCA, in contrast to SspCA, probed using molecular dynamics simulations. Our simulations, carried out at different temperatures, indicate the presence of efficient proton shuttle between the active zinc centre and His64 residue in the two enzymes. The proton accepting His64 residue was identified to have in and out conformations with the in conformations being supportive to proton acceptance. Our simulations show a large population of in conformations in SazCA making the enzyme exhibit an exceptional activity. The RMSF and H-bonds analysis confirmed the role of His2 and His207 in supporting the attainment of in conformations in SazCA resulting in exceptional activity. Communicated by Ramaswamy H. Sarma
Shashi Kumar, N. N. Subrahmanyeswara Rao, K. S. S. V. Prasad Reddy, Manjusha C. Padole, and Parag A. Deshpande
Royal Society of Chemistry (RSC)
QM/MM analysis of orotate-mimetic inhibitors of orotate phosphoribosyltransferase revealed 4-Hydroxy-6-methylpyridin-2(1H)-one be the best inhibitor among the tested ones for the inhibition of OPRT action.
Manju Verma, V. Sai Phani Kumar, Shashi Kumar, and Parag A. Deshpande
Royal Society of Chemistry (RSC)
Inspired by the recent experimental reports on boron containing compounds to be active and biomimetic for carbon capture, we report the mechanistic details of CO2 hydration activities of boronic acids using density functional theory calculations.
Shashi Kumar and Parag A. Deshpande
Public Library of Science (PLoS)
Molecular basis of protein stability at different temperatures is a fundamental problem in protein science that is substantially far from being accurately and quantitatively solved as it requires an explicit knowledge of the temperature dependence of folding free energy of amino acid residues. In the present study, we attempted to gain insights into the thermodynamic stability of SazCA and its implications on protein folding/unfolding. We report molecular dynamics simulations of water solvated SazCA in a temperature range of 293-393 K to study the relationship between the thermostability and flexibility. Our structural analysis shows that the protein maintains the highest structural stability at 353 K and the protein conformations are highly flexible at temperatures above 353 K. Larger exposure of hydrophobic surface residues to the solvent medium for conformations beyond 353 K were identified from H-bond analysis. Higher number of secondary structure contents exhibited by SazCA at 353 K corroborated the conformations at 353 K to exhibit the highest thermal stability. The analysis of thermodynamics of protein stability revealed that the conformations that denature at higher melting temperatures tend to have greater maximum thermal stability. Our analysis shows that 353 K conformations have the highest melting temperature, which was found to be close to the experimental optimum temperature. The enhanced protein stability at 353 K due the least value of heat capacity at unfolding suggested an increase in folding. Comparative Gibbs free energy analysis and funnel shaped energy landscape confirmed a transition in folding/unfolding pathway of SazCA at 353 K.
Shashi Kumar, Deepak Seth, and Parag Arvind Deshpande
Wiley
AbstractThe present study examined the structure and dynamics of the most active and thermostable carbonic anhydrase, SazCA, probed using molecular dynamics simulations. The molecular system was described by widely used biological force‐fields (AMBER, CHARMM22, CHARMM36, and OPLS‐AA) in conjunction with TIP3P water model. The comparison of molecular dynamics simulation results suggested AMBER to be a suitable choice to describe the structure and dynamics of SazCA. In addition to this, we also addressed the effect of temperature on the stability of SazCA. We performed molecular dynamics simulations at 313, 333, 353, 373, and 393 K to study the relationship between thermostability and flexibility in SazCA. The amino acid residues VAL98, ASN99, GLY100, LYS101, GLU145, and HIS207 were identified as the most flexible residues from root‐mean‐square fluctuations. The salt bridge analysis showed that ion‐pairs ASP113‐LYS81, ASP115‐LYS81, ASP115‐LYS114, GLU144‐LYS143, and GLU144‐LYS206, were responsible for the compromised thermal stability of SazCA.
Tamoghna Saha, Shashi Kumar, and Soubhik Kumar Bhaumik
Elsevier BV
Tamoghna Saha, Shashi Kumar, and Soubhik Kumar Bhaumik
Springer Science and Business Media LLC
Rawel Singh, Aditya Prakash, Shashi Kumar Dhiman, Bhavya Balagurumurthy, Ajay K. Arora, S.K. Puri, and Thallada Bhaskar
Elsevier BV