Thirumoorthy Krishnan | VIT University (original) (raw)
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Papers by Thirumoorthy Krishnan
Physical Chemistry Chemical Physics, 2022
Planar tetracoordinate carbon (ptC) and pentacoordinate carbon (ppC) with 20 valence electrons.
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Journal of Molecular Structure, 2017
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Journal of Molecular Structure-theochem, Sep 1, 2007
This paper reports the study on the catalytic effect of a single water molecule on the peptide bo... more This paper reports the study on the catalytic effect of a single water molecule on the peptide bond formation in l-alanine dipeptide using ab-initio methods at the HF/6-31G∗ level of theory and comparison with the corresponding noncatalyzed reaction. Both concerted and stepwise mechanisms are studied. Zero point corrections are made and thermodynamic parameters are evaluated. The barrier heights are systematically
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Journal of Physical Chemistry B, Apr 12, 2006
In the present work, we compare the intermolecular energy surfaces of the alanine molecule in its... more In the present work, we compare the intermolecular energy surfaces of the alanine molecule in its neutral and zwitterionic state using ab initio theory (HF/6-311++G) as a function of mutual orientation. Starting from the optimized structures of the nonbonded homochiral (l-l) and heterochiral (d-l) pairs of molecules, the energy surfaces are studied with rigid geometry by varying the distance and orientation. The potential energy surfaces of the l-l and d-l pairs are found to be dissimilar and reflect the underlying chirality of the homochiral pair and racemic nature of the heterochiral pair. The intermolecular energy surface of the l-l pair is more favorable than the corresponding energy surface of the d-l pair. The study, for the first time, reveals clear homochiral preference without use of parameters, which was unobserved in previous detailed simulations but predicted by theory. The electrostatic interaction further augments the chiral discrimination. The basis set superposition error (BSSE) corrected results show enhanced discrimination. Use of higher-level Møller-Plesset perturbation theory (MP2) and further BSSE correction do not change the conclusions made at the Hartree-Fock (HF) level. The major conclusions based on HF and MP2 level calculations remain unaltered when the calculations of the potential energy surfaces for the neutral and zwitterionic pairs are repeated using the density functional theory (DFT) (B3LYP/6-311++G). The observed orientation dependence has significance in the biological chiral recognition as well as peptide synthesis at the peptidyl transferase center where the amino terminal and peptidyl terminal undergo mutual rotatory motion.
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Langmuir, May 26, 2007
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Cancer Research, Oct 31, 2017
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Langmuir, May 12, 2006
Recent studies have shown that dipalmitoyl phosphatidyl choline (DPPC) monolayers respond coopera... more Recent studies have shown that dipalmitoyl phosphatidyl choline (DPPC) monolayers respond cooperatively to the presence of dipyridamole (DIP) guest molecules even at small concentrations, which is a signature of molecular recognition. Using semiempirical quantum mechanical calculations for the DIP-DPPC system, we show that the incorporation of DIP causes large changes in the vertical dipole moment of the DIP-DPPC system, which can explain why measurable changes in surface potential are observed experimentally even at very low DIP concentrations. The calculations are also consistent with the anomalous concentration dependence of the surface pressure and surface potential isotherms for DIP-DPPC monolayers. Rather than saturation or a continuous increase in the effects caused by the incorporation of increasing amounts of DIP, the experimentally observed inversion in the behavior of the surface potential as the DIP concentration reaches 0.5 mol % would be caused by a change in DIP conformation, from a vertical arrangement for the DIP rings to a horizontal or intermediate arrangement. The strong dipolar interactions indicated in the calculations may also be the origin of the drastic changes in monolayer morphology seen in fluorescence microscopy images, with triskellion-shaped domains being formed for condensed DIP-DPPC monolayers.
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Clinical Cancer Research, Apr 30, 2017
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Journal of Physical Chemistry B, Jun 21, 2005
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International Journal of Radiation Oncology Biology Physics, Oct 1, 2013
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Journal of Physical Chemistry B, Aug 1, 2007
Experimental studies have shown that peptide synthesis in ribosome exhibits a homochiral preferen... more Experimental studies have shown that peptide synthesis in ribosome exhibits a homochiral preference. We present, for the first time, an analysis of the origin of the phenomenon using hybrid quantum chemical studies based on a model of peptidyl transferase center from the crystal structure of the ribosomal part of Haloarcula marismortui. The study quantitatively shows that the observed homochiral preference is due to the difference in the nonbonded interaction between amino acids at the A- and P-terminals as well as due to the difference in interaction with the U2620 residue. A major part of the discrimination comes from the variation of nonbonded interaction of rotating A-terminal during the approach of the former toward the P-terminal. The difference indicates that, during the rotatory motion between A- and P-terminals for the proximal positioning of the reactant for reaction to occur, the interaction for a L-L pair is far less repulsive compared to the same process for a D-L pair. The activation barriers for L-L and D-L pairs of the neutral state of phenylalanine leading to corresponding dipeptides are also compared. The corresponding difference in rate constants is 40-fold. The study provides an understanding of how preferred addition of L-L pairs of amino acids rather than D-L pairs leads to retention of homochirality in peptides.
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Chemistry, May 9, 2023
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Chemistry, Dec 31, 2020
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Chemical Physics Letters, Oct 1, 2005
Abstract 1-Octadecylcytosine (C 18 Cyt) with guanine nucleoside pairs develop spiral shaped domai... more Abstract 1-Octadecylcytosine (C 18 Cyt) with guanine nucleoside pairs develop spiral shaped domains of both handedness in the monolayers composed of pure enantiomer. Globally optimized structures of the pair with different puckering of oxy and deoxy pairs are studied using hybrid quantum mechanical–molecular mechanical theory and the mutual azimuthal orientations for two molecular pairs are investigated. Both left-handedness and right-handedness of domain curvature for oxy as well as deoxy pairs are predicted by theoretical calculations in nice agreement with experiment. The present study definitively correlates the molecular chirality of sugar ring with the domain morphology of nucleic acid mimetic systems.
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Physical Chemistry Chemical Physics, 2022
Chemical intuition yields the second low-lying isomer after AUTOMATON found the global minimum an... more Chemical intuition yields the second low-lying isomer after AUTOMATON found the global minimum and few other low-lying isomers.
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Langmuir, Jul 24, 2008
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The Journal of Physical Chemistry A
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Supporting Figures Figure S1. Extracellular and intracellular metabolites of commercially availab... more Supporting Figures Figure S1. Extracellular and intracellular metabolites of commercially available and patient derived GBM cells and NHAs Figure S2. Total and extracted ion chromatograms of intracellular metabolites Figure S3. Total and extracted ion chromatograms of extracellular metabolites Figure S4. Targeted analysis MS/MS product ion spectrum of methionine Figure S5. Targeted analysis MS/MS product ion spectrum of tryptophan Figure S6. Targeted analysis MS/MS product ion spectrum of kynurenine Figure S7. Targeted analysis MS/MS product ion spectrum of MTA Figure S8. Total ion chromatogram and multiple reaction monitoring of different concentrations of methionine Figure S9. Total ion chromatogram and multiple reaction monitoring of different concentrations of kynurenine Figure S10. Key metabolites in methionine pathway Figure S11. Calibration Curve and Multiple Reaction Monitoring of SAM and SAH Figure S12. Key metabolites in tryptophan pathway Figure S13. Insilico analysis - Connecting metabolome and proteome in GBM cells Figure S14. Densitometric quantification of the chemiluminescence signals
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Molecules
Mutations in homodimeric isocitrate dehydrogenase (IDH) enzymes at specific arginine residues res... more Mutations in homodimeric isocitrate dehydrogenase (IDH) enzymes at specific arginine residues result in the abnormal activity to overproduce D-2 hydroxyglutarate (D-2HG), which is often projected as solid oncometabolite in cancers and other disorders. As a result, depicting the potential inhibitor for D-2HG formation in mutant IDH enzymes is a challenging task in cancer research. The mutation in the cytosolic IDH1 enzyme at R132H, especially, may be associated with higher frequency of all types of cancers. So, the present work specifically focuses on the design and screening of allosteric site binders to the cytosolic mutant IDH1 enzyme. The 62 reported drug molecules were screened along with biological activity to identify the small molecular inhibitors using computer-aided drug design strategies. The designed molecules proposed in this work show better binding affinity, biological activity, bioavailability, and potency toward the inhibition of D-2HG formation compare to the report...
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Physical Chemistry Chemical Physics, 2022
Planar tetracoordinate carbon (ptC) and pentacoordinate carbon (ppC) with 20 valence electrons.
Bookmarks Related papers MentionsView impact
Journal of Molecular Structure, 2017
Bookmarks Related papers MentionsView impact
Journal of Molecular Structure-theochem, Sep 1, 2007
This paper reports the study on the catalytic effect of a single water molecule on the peptide bo... more This paper reports the study on the catalytic effect of a single water molecule on the peptide bond formation in l-alanine dipeptide using ab-initio methods at the HF/6-31G∗ level of theory and comparison with the corresponding noncatalyzed reaction. Both concerted and stepwise mechanisms are studied. Zero point corrections are made and thermodynamic parameters are evaluated. The barrier heights are systematically
Bookmarks Related papers MentionsView impact
Journal of Physical Chemistry B, Apr 12, 2006
In the present work, we compare the intermolecular energy surfaces of the alanine molecule in its... more In the present work, we compare the intermolecular energy surfaces of the alanine molecule in its neutral and zwitterionic state using ab initio theory (HF/6-311++G) as a function of mutual orientation. Starting from the optimized structures of the nonbonded homochiral (l-l) and heterochiral (d-l) pairs of molecules, the energy surfaces are studied with rigid geometry by varying the distance and orientation. The potential energy surfaces of the l-l and d-l pairs are found to be dissimilar and reflect the underlying chirality of the homochiral pair and racemic nature of the heterochiral pair. The intermolecular energy surface of the l-l pair is more favorable than the corresponding energy surface of the d-l pair. The study, for the first time, reveals clear homochiral preference without use of parameters, which was unobserved in previous detailed simulations but predicted by theory. The electrostatic interaction further augments the chiral discrimination. The basis set superposition error (BSSE) corrected results show enhanced discrimination. Use of higher-level Møller-Plesset perturbation theory (MP2) and further BSSE correction do not change the conclusions made at the Hartree-Fock (HF) level. The major conclusions based on HF and MP2 level calculations remain unaltered when the calculations of the potential energy surfaces for the neutral and zwitterionic pairs are repeated using the density functional theory (DFT) (B3LYP/6-311++G). The observed orientation dependence has significance in the biological chiral recognition as well as peptide synthesis at the peptidyl transferase center where the amino terminal and peptidyl terminal undergo mutual rotatory motion.
Bookmarks Related papers MentionsView impact
Langmuir, May 26, 2007
Bookmarks Related papers MentionsView impact
Cancer Research, Oct 31, 2017
Bookmarks Related papers MentionsView impact
Langmuir, May 12, 2006
Recent studies have shown that dipalmitoyl phosphatidyl choline (DPPC) monolayers respond coopera... more Recent studies have shown that dipalmitoyl phosphatidyl choline (DPPC) monolayers respond cooperatively to the presence of dipyridamole (DIP) guest molecules even at small concentrations, which is a signature of molecular recognition. Using semiempirical quantum mechanical calculations for the DIP-DPPC system, we show that the incorporation of DIP causes large changes in the vertical dipole moment of the DIP-DPPC system, which can explain why measurable changes in surface potential are observed experimentally even at very low DIP concentrations. The calculations are also consistent with the anomalous concentration dependence of the surface pressure and surface potential isotherms for DIP-DPPC monolayers. Rather than saturation or a continuous increase in the effects caused by the incorporation of increasing amounts of DIP, the experimentally observed inversion in the behavior of the surface potential as the DIP concentration reaches 0.5 mol % would be caused by a change in DIP conformation, from a vertical arrangement for the DIP rings to a horizontal or intermediate arrangement. The strong dipolar interactions indicated in the calculations may also be the origin of the drastic changes in monolayer morphology seen in fluorescence microscopy images, with triskellion-shaped domains being formed for condensed DIP-DPPC monolayers.
Bookmarks Related papers MentionsView impact
Clinical Cancer Research, Apr 30, 2017
Bookmarks Related papers MentionsView impact
Journal of Physical Chemistry B, Jun 21, 2005
Bookmarks Related papers MentionsView impact
International Journal of Radiation Oncology Biology Physics, Oct 1, 2013
Bookmarks Related papers MentionsView impact
Journal of Physical Chemistry B, Aug 1, 2007
Experimental studies have shown that peptide synthesis in ribosome exhibits a homochiral preferen... more Experimental studies have shown that peptide synthesis in ribosome exhibits a homochiral preference. We present, for the first time, an analysis of the origin of the phenomenon using hybrid quantum chemical studies based on a model of peptidyl transferase center from the crystal structure of the ribosomal part of Haloarcula marismortui. The study quantitatively shows that the observed homochiral preference is due to the difference in the nonbonded interaction between amino acids at the A- and P-terminals as well as due to the difference in interaction with the U2620 residue. A major part of the discrimination comes from the variation of nonbonded interaction of rotating A-terminal during the approach of the former toward the P-terminal. The difference indicates that, during the rotatory motion between A- and P-terminals for the proximal positioning of the reactant for reaction to occur, the interaction for a L-L pair is far less repulsive compared to the same process for a D-L pair. The activation barriers for L-L and D-L pairs of the neutral state of phenylalanine leading to corresponding dipeptides are also compared. The corresponding difference in rate constants is 40-fold. The study provides an understanding of how preferred addition of L-L pairs of amino acids rather than D-L pairs leads to retention of homochirality in peptides.
Bookmarks Related papers MentionsView impact
Chemistry, May 9, 2023
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Chemistry, Dec 31, 2020
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Chemical Physics Letters, Oct 1, 2005
Abstract 1-Octadecylcytosine (C 18 Cyt) with guanine nucleoside pairs develop spiral shaped domai... more Abstract 1-Octadecylcytosine (C 18 Cyt) with guanine nucleoside pairs develop spiral shaped domains of both handedness in the monolayers composed of pure enantiomer. Globally optimized structures of the pair with different puckering of oxy and deoxy pairs are studied using hybrid quantum mechanical–molecular mechanical theory and the mutual azimuthal orientations for two molecular pairs are investigated. Both left-handedness and right-handedness of domain curvature for oxy as well as deoxy pairs are predicted by theoretical calculations in nice agreement with experiment. The present study definitively correlates the molecular chirality of sugar ring with the domain morphology of nucleic acid mimetic systems.
Bookmarks Related papers MentionsView impact
Physical Chemistry Chemical Physics, 2022
Chemical intuition yields the second low-lying isomer after AUTOMATON found the global minimum an... more Chemical intuition yields the second low-lying isomer after AUTOMATON found the global minimum and few other low-lying isomers.
Bookmarks Related papers MentionsView impact
Langmuir, Jul 24, 2008
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The Journal of Physical Chemistry A
Bookmarks Related papers MentionsView impact
Bookmarks Related papers MentionsView impact
Supporting Figures Figure S1. Extracellular and intracellular metabolites of commercially availab... more Supporting Figures Figure S1. Extracellular and intracellular metabolites of commercially available and patient derived GBM cells and NHAs Figure S2. Total and extracted ion chromatograms of intracellular metabolites Figure S3. Total and extracted ion chromatograms of extracellular metabolites Figure S4. Targeted analysis MS/MS product ion spectrum of methionine Figure S5. Targeted analysis MS/MS product ion spectrum of tryptophan Figure S6. Targeted analysis MS/MS product ion spectrum of kynurenine Figure S7. Targeted analysis MS/MS product ion spectrum of MTA Figure S8. Total ion chromatogram and multiple reaction monitoring of different concentrations of methionine Figure S9. Total ion chromatogram and multiple reaction monitoring of different concentrations of kynurenine Figure S10. Key metabolites in methionine pathway Figure S11. Calibration Curve and Multiple Reaction Monitoring of SAM and SAH Figure S12. Key metabolites in tryptophan pathway Figure S13. Insilico analysis - Connecting metabolome and proteome in GBM cells Figure S14. Densitometric quantification of the chemiluminescence signals
Bookmarks Related papers MentionsView impact
Molecules
Mutations in homodimeric isocitrate dehydrogenase (IDH) enzymes at specific arginine residues res... more Mutations in homodimeric isocitrate dehydrogenase (IDH) enzymes at specific arginine residues result in the abnormal activity to overproduce D-2 hydroxyglutarate (D-2HG), which is often projected as solid oncometabolite in cancers and other disorders. As a result, depicting the potential inhibitor for D-2HG formation in mutant IDH enzymes is a challenging task in cancer research. The mutation in the cytosolic IDH1 enzyme at R132H, especially, may be associated with higher frequency of all types of cancers. So, the present work specifically focuses on the design and screening of allosteric site binders to the cytosolic mutant IDH1 enzyme. The 62 reported drug molecules were screened along with biological activity to identify the small molecular inhibitors using computer-aided drug design strategies. The designed molecules proposed in this work show better binding affinity, biological activity, bioavailability, and potency toward the inhibition of D-2HG formation compare to the report...
Bookmarks Related papers MentionsView impact