The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform

R Rajasekaran - One of the best experts on this subject based on the ideXlab platform.

  • In Silico Template Selection of Short Antimicrobial Peptide Viscotoxin for Improving Its Antimicrobial Efficiency in Development of Potential Therapeutic Drugs
    Applied Biochemistry and Biotechnology, 2017
    Co-Authors: B Senthilkumar, R Rajasekaran
    Abstract:

    Rapid increase in antibiotic resistance has posed a worldwide threat, due to increased mortality, morbidity, and expenditure caused by antibiotic-resistant microbes. Recent development of the antimicrobial peptides like viscotoxin (Vt) has been successfully comprehended as a substitute for classical antibiotics. A structurally stable peptide, Vt can enhance antimicrobial property and can be used for various developmental purposes. Thus, structural stability among the antimicrobial peptides, Vt A1 (3C8P), A2 (1JMN), A3 (1ED0), B (1JMP), and C (1ORL) of Viscus album was computationally analyzed. In specific, the static confirmation of VtA3 showed high number of intramolecular interactions, along with an increase in hydrophobicity than others comparatively. Further, conformational sampling was used to analyze various geometrical parameters such as root mean Square deviation, root mean Square Fluctuation, radius of gyration, and ovality which also revealed the structural stability of VtA3. Moreover, the statistically validated contours of surface area, lipophilicity, and distance constraints of disulfide bonds also supported the priority of VtA3 with respect to stability. Finally, the functional activity of peptides was accessed by computing their free energy of membrane association and membrane interactions, which defined VtA3 as functionally stable. Currently, peptide-based antibiotics and nanoparticles have attracted the pharmaceutical industries for their potential therapeutic applications. Thereby, it is proposed that viscotoxin A3 (1ED0) could be used as a preeminent template for scaffolding potentially efficient antimicrobial peptide-based drugs and nanomaterials in future.

  • Analysis of the Structural Stability Among Cyclotide Members Through Cystine Knot Fold that Underpins Its Potential Use as a Drug Scaffold
    International Journal of Peptide Research and Therapeutics, 2017
    Co-Authors: B Senthilkumar, R Rajasekaran
    Abstract:

    Recent emergence of plant derived peptide cyclotides, characterized with a cyclized head-to-tail backbone and three disulfide bonds forming cyclic cystine knot, has advanced the field of biopharmaceutics to next level. This conserved structural feature of cyclotides holds responsible for its outstanding resistance towards thermal, chemical and enzymatic degradation. Besides, the cyclotides are preferred widely in current research to develop them as potent peptide therapeutics, where the improvement of structural stability is a demanding task in pharmaceutical firm. Hence, in this work, the structural stability of six cyclotides of kalata family (kalata B1, kalata B2, kalata B5, kalata B7, kalata B8 and kalata B12) was investigated. Among all, maximum number of intra-molecular interactions was observed only in kalata B1 (kB1). In addition, geometrical observables using conformational sampling of six kalata cyclotides also revealed that kB1 exhibited statistically significant structural stability in terms of contours of root mean Square Fluctuation, gyration radius, ovality and surface area (polar and non-polar). Furthermore, the distance of disulfide bridges (S–S within 2.2 Å) also confirmed that kB1 achieved maximum strength in terms of structural stability and accomplished remarkable functionality in terms of ovality as compared to other five kalata cyclotides. Accordingly, kB1 could be demonstrated as a stable template for the advancement of peptide therapeutics.

  • in silico template selection of in vitro evolved kalata b1 of oldenlandia affinis for scaffolding peptide based drug design
    Journal of Cellular Biochemistry, 2016
    Co-Authors: B Senthilkumar, Prakash Kumar, R Rajasekaran
    Abstract:

    : Structural stability of Oldenlandia affinis cyclotide, kalata B1 of native (1NB1) and two mutants 2F2I ([P20D, V21K] kB1) and 2F2J ([W19K, P20N, V21K] kB1) was investigated. Single model analysis showed high number of intra-molecular interactions followed by more proportion of beta sheet contents in [P20D, V21K] kB1 as compared to that of native and the other mutant of kalata B1. Further, the modern conformational sampling approach, an alternate to classical molecular dynamics was introduced, which revealed that the [P20D, V21K] kB1 was identified as structurally stable one, substantiated by various structural events viz., root mean Square deviation, root mean Square Fluctuation, and angular deviation by Ramachandran plot. Moreover, the statistically validated contours of polar surface area, hydrogen bond distribution and the distance of disulfide bridges also supported the priority of [P20D, V21K] kB1 with respect to stability. From this work, it is proposed that the [P20D, V21K] kB1 (2F2I) could be the best template for scaffolding peptide based drug design.

B Senthilkumar - One of the best experts on this subject based on the ideXlab platform.

  • In Silico Template Selection of Short Antimicrobial Peptide Viscotoxin for Improving Its Antimicrobial Efficiency in Development of Potential Therapeutic Drugs
    Applied Biochemistry and Biotechnology, 2017
    Co-Authors: B Senthilkumar, R Rajasekaran
    Abstract:

    Rapid increase in antibiotic resistance has posed a worldwide threat, due to increased mortality, morbidity, and expenditure caused by antibiotic-resistant microbes. Recent development of the antimicrobial peptides like viscotoxin (Vt) has been successfully comprehended as a substitute for classical antibiotics. A structurally stable peptide, Vt can enhance antimicrobial property and can be used for various developmental purposes. Thus, structural stability among the antimicrobial peptides, Vt A1 (3C8P), A2 (1JMN), A3 (1ED0), B (1JMP), and C (1ORL) of Viscus album was computationally analyzed. In specific, the static confirmation of VtA3 showed high number of intramolecular interactions, along with an increase in hydrophobicity than others comparatively. Further, conformational sampling was used to analyze various geometrical parameters such as root mean Square deviation, root mean Square Fluctuation, radius of gyration, and ovality which also revealed the structural stability of VtA3. Moreover, the statistically validated contours of surface area, lipophilicity, and distance constraints of disulfide bonds also supported the priority of VtA3 with respect to stability. Finally, the functional activity of peptides was accessed by computing their free energy of membrane association and membrane interactions, which defined VtA3 as functionally stable. Currently, peptide-based antibiotics and nanoparticles have attracted the pharmaceutical industries for their potential therapeutic applications. Thereby, it is proposed that viscotoxin A3 (1ED0) could be used as a preeminent template for scaffolding potentially efficient antimicrobial peptide-based drugs and nanomaterials in future.

  • Analysis of the Structural Stability Among Cyclotide Members Through Cystine Knot Fold that Underpins Its Potential Use as a Drug Scaffold
    International Journal of Peptide Research and Therapeutics, 2017
    Co-Authors: B Senthilkumar, R Rajasekaran
    Abstract:

    Recent emergence of plant derived peptide cyclotides, characterized with a cyclized head-to-tail backbone and three disulfide bonds forming cyclic cystine knot, has advanced the field of biopharmaceutics to next level. This conserved structural feature of cyclotides holds responsible for its outstanding resistance towards thermal, chemical and enzymatic degradation. Besides, the cyclotides are preferred widely in current research to develop them as potent peptide therapeutics, where the improvement of structural stability is a demanding task in pharmaceutical firm. Hence, in this work, the structural stability of six cyclotides of kalata family (kalata B1, kalata B2, kalata B5, kalata B7, kalata B8 and kalata B12) was investigated. Among all, maximum number of intra-molecular interactions was observed only in kalata B1 (kB1). In addition, geometrical observables using conformational sampling of six kalata cyclotides also revealed that kB1 exhibited statistically significant structural stability in terms of contours of root mean Square Fluctuation, gyration radius, ovality and surface area (polar and non-polar). Furthermore, the distance of disulfide bridges (S–S within 2.2 Å) also confirmed that kB1 achieved maximum strength in terms of structural stability and accomplished remarkable functionality in terms of ovality as compared to other five kalata cyclotides. Accordingly, kB1 could be demonstrated as a stable template for the advancement of peptide therapeutics.

  • in silico template selection of in vitro evolved kalata b1 of oldenlandia affinis for scaffolding peptide based drug design
    Journal of Cellular Biochemistry, 2016
    Co-Authors: B Senthilkumar, Prakash Kumar, R Rajasekaran
    Abstract:

    : Structural stability of Oldenlandia affinis cyclotide, kalata B1 of native (1NB1) and two mutants 2F2I ([P20D, V21K] kB1) and 2F2J ([W19K, P20N, V21K] kB1) was investigated. Single model analysis showed high number of intra-molecular interactions followed by more proportion of beta sheet contents in [P20D, V21K] kB1 as compared to that of native and the other mutant of kalata B1. Further, the modern conformational sampling approach, an alternate to classical molecular dynamics was introduced, which revealed that the [P20D, V21K] kB1 was identified as structurally stable one, substantiated by various structural events viz., root mean Square deviation, root mean Square Fluctuation, and angular deviation by Ramachandran plot. Moreover, the statistically validated contours of polar surface area, hydrogen bond distribution and the distance of disulfide bridges also supported the priority of [P20D, V21K] kB1 with respect to stability. From this work, it is proposed that the [P20D, V21K] kB1 (2F2I) could be the best template for scaffolding peptide based drug design.

Takahide Yokoi - One of the best experts on this subject based on the ideXlab platform.

  • In silico and in vitro Approaches to Elucidate the Thermal Stability of Human UDP-glucuronosyltransferase UGT 1A9
    Drug Metabolism and Pharmacokinetics, 2009
    Co-Authors: Miki Nakajima, T. Yamamoto, Hiroshi Nagao, Takahide Yokoi
    Abstract:

    Summary: UDP-Glucuronosyltransferases (UGTs) are predominant drug metabolizing enzymes in the liver and extrahepatic tissues. Human UGT1A9 is uniquely stable against heat treatment. To understand the u- nique properties of UGT1A9, the three-dimensional structure was constructed by homologymodeling using a crystal structure of TDP-epi-vancosaminyltransferase as template. Sequence alignment analysis revealed that 13 amino acid residues (Arg42, Lys91, Ala92, Tyr106, Gly111, Tyr113, Asp115, Asn152, Leu173, Leu219, His221, Arg222, and Glu241) are unique to UGT1A9 as compared with UGT1A7, UGT1A8 and UGT1A10. To examine the roles of these residues in the conformational stability of UGT1A9, molecular dy- namics simulation of the structures was carried out at 310 K and 360 K in aqueous solution for 3.0 nanose- conds. Root mean Square deviation analyses revealed that Arg42, Leu173, Leu219, His221 and Arg222 were responsible for the thermal stability. Rootmean Square Fluctuation analyses and a dynamical cross corre- lation map revealed that Lys91, Ala92, Tyr106, Gly111, Tyr113, Asp115, Leu219, His221, Arg222 and Glu241 were responsible for the thermal stability. In vitro study usingmutants of these residues demonstrated that all these amino acidsmay be collectively involved in the thermal stability of UGT1A9. The results present- ed here provide a molecular basis for the thermal stability of human UGT1A9.

M. M. Korovushkin - One of the best experts on this subject based on the ideXlab platform.

  • Lower subband splitting and superconductivity of 2D Hubbard fermions with strong intersite correlations
    Bulletin of the Russian Academy of Sciences: Physics, 2012
    Co-Authors: V. V. Val’kov, M. M. Korovushkin
    Abstract:

    The effect of the strong intersite Coulomb correlations on the formation of an electron structure in the Shubin-Vonsowsky model in the regime of strong one-site correlations is studied. The results reveal a split-off band of the Fermi states. The spectral intensity of this band grows with the enhancement of the doping level and is determined by the mean-Square Fluctuation of occupation numbers. This changes the structure of the electron density of states qualitatively.

  • Hubbard fermions band splitting at the strong intersite Coulomb interaction
    arXiv: Strongly Correlated Electrons, 2009
    Co-Authors: Valery V. Val ' Kovand, M. M. Korovushkin
    Abstract:

    The effect of the strong intersite Coulomb correlations on the formation of the electron structure of the t-V-model has been studied. A qualitatively new result has been obtained which consists in the occurrence of a split-off band of the Fermi states. The spectral intensity of this band increases with the enhancement of a doping level and is determined by the mean-Square Fluctuation of the occupation numbers. This leads to the qualitative change in the structure of the electron density of states.

Nobuhiro Go - One of the best experts on this subject based on the ideXlab platform.

  • comparison of normal mode analyses on a small globular protein in dihedral angle space and cartesian coordinate space
    Biophysical Chemistry, 1994
    Co-Authors: Akio Kitao, Steven Hayward, Nobuhiro Go
    Abstract:

    Abstract Normal mode analyses on the protein, bovine pancreatic trypsin inhibitor, in dihedral angle space and Cartesian coordinate space are compared. In Cartesian coordinate space it is found that modes of frequencies lower than 30 cm−1 contribute 80% of the total mean-Square Fluctuation and are represented almost completely by motions in the dihedral angles. Bond angle and length Fluctuations dominate in modes above 200 cm−1, but contribute less than 2% to the total mean-Square Fluctuation. In the low-frequency modes a good correspondence between patterns of atomic displacements was found, but on average the root-mean-Square Fluctuations of the Cartesian coordinate modes are 13% greater than their dihedral angle counterparts. The main effect of Fluctuations in the bond angles and lengths, therefore, is to allow the dihedral angles to become more flexible. As the important subspaces determined from the two methods overlap considerably, dihedral angle space analysis can be applied to proteins too large for Cartesian coordinate space analysis