Rational Labs Pvt. Ltd.

Hyderabad andhra Pradesh, India

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Hyderabad andhra Pradesh, India

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The kinetics of oxidation of tris(1,10-phenanthroline)iron(II) and tris(2,2'-bipyridine)iron(II) by chromium(VI) in the presence of 1,10-phenanthroline and 2,2'-bipyridine has been studied in sulphuric acid medium. The order of the reaction is unity both in substrate, oxidant and fractional with hydrogen ion. The catalyst (2,2'-bipyridine/1,10-phenanthroline) accelerates the reaction and the order with respect to [catalyst] is fractional. All these reactions follow the Michaelis-Menton behaviour and rate increases with ionic strength. All the reactions obey the following rate law and a generalised mechanism was proposed: rate = k[Cr(VI)]T K1 K 2 [catalyst] [H+]}/1 + K1 [catalyst] + K 1K2 [catalyst][H+] [Fe(L)3 2+].


Reddy R.N.,Rational Labs Pvt. Ltd. | Anipindi N.R.,Andhra University
Oxidation Communications | Year: 2011

The kinetics of ruthenium(III)-catalysed oxidation reaction of bis(2,2′,6′,2″-terpyridine)iron(II) by bromate in acetate buffers in the pH range 3.6-5.6 was studied spectrophotometrically. The reaction exhibits first order each in [substrate], [oxidant] and [ruthenium(III)]. Hydrogen ion has no significant effect and ionic strength increases the rate of the reaction. A suitable mechanism has been proposed to explain the kinetic data.


Reddy R.N.,Rational Labs Pvt. Ltd | Mutyala R.R.,Rational Labs Pvt. Ltd | Mutyala R.R.,RR Labs Inc. | Aparoy P.,University of Hyderabad | And 2 more authors.
Journal of Molecular Modeling | Year: 2010

Since the human body for many reasons can adapt and become resistant to drugs, it is important to develop and validate computer aided drug design (CADD) methods that could help predict binding affinity changes that can result from these resistant enzymes. The free energy perturbation (FEP) methodology is the most accurate means of estimating relative binding affinities between inhibitors and protein variants. In this paper, we describe the role played by hydrophobic residues lining the active site region, particularly 79 Ile and 176 Phe, in the binding of methotrexate to the Escherichia coli (E. coli) thymidylate synthase (TS) enzyme, using the thermodynamic cycle perturbation (TCP) approach. The computed binding free energy differences on the binding of methotrexate to the native and some mutant E. coli TS structures have been compared with experimental results. Computationally, four different 'mutations' have been simulated on the TS enzyme with methotrexate (MTX): 79 Ile∈→∈ 79 Val; 79 Ile → 79 Ala; 79 Ile → 79 Leu; and 176 Phe∈→∈ 176 Ile. The calculated results indicate that in each of these cases, the native residues ( 79 Ile and 176 Phe) interact more favorably with methotrexate than the mutant residues and these results are corroborated by experimental measurements. Binding preference to wild type residues can be rationalized in terms of their better hydrophobic contacts with the phenyl ring of methotrexate. © 2009 Springer-Verlag.


Reddy K.V.,C S R Sarma College | Satyanarayana T.,P.A. College | Anipindi N.R.,Andhra University | Reddy R.N.,Andhra University | Reddy R.N.,Rational Labs Pvt. Ltd.
Oxidation Communications | Year: 2011

The kinetics and mechanism of Ag(I)-catalysed oxidation of bis(2,2′,6′,2″terpyridine)iron(II) by persulphate in acetate buffers in the pH range 3.6-5.6 were studied by spectrophotometric method. The reaction follows first order with respect to the substrate and the oxidant. The rate of the reaction increases with [Ag(I)] and the order with respect to [Ag(I)] is fractional. Hydrogen ion and terpyridine have no significant effect on the rate. Ionic strength decreases the rate of the reaction indicating that the rate-limiting step is between ions of opposite charges. It was also observed that the reaction in acetate buffers is appreciably catalysed by silver(I) and the role of the catalyst has been indicated to be either via the Ag(I)/Ag(II) redox cycle or the intermediate complex of Ag(I)-peroxyacid. A suitable mechanism was proposed and the specific rate constants were evaluated.


Aparoy P.,University of Hyderabad | Reddy R.N.,Rational Labs Pvt. Ltd | Guruprasad L.,University of Hyderabad | Reddanna P.,University of Hyderabad
Letters in Drug Design and Discovery | Year: 2010

Acidic mammalian chitinase (AMCase) is a potential target for inflammatory disorders, including Th2-driven diseases such as asthma, allergy, atopic dermatitis and allergic rhinitis. AMCase, along with human chitotriosidase (HCHT) are the two human chitinases that are enzymatically active. In this study, a comparative analysis of AMCase (PDB id. 3FY1) was done with that of HCHT (PDB id.1WAW) and Aspergillus fumigatus chitinase (PDB id.1W9U) to identify differences in the binding site topology and interacting residues. Argadin, a natural inhibitor of chitinases, was docked into the active site of AMCase. All the proteins have the DXDXE motif, like other family 18 chitinases. There is a crucial difference in the stacking interactions in chitinases. The chitinase of Aspergillus fumigatus (AfchiB1) is unique in having Phe251 compared to Trp in others at the same position. Arg269 forms strong hydrogen bonds with argadin in HCHT and AfchiB1 but not in AMCase. Many crucial differences between the binding sites of AMCase and HCHT were identified. As AMCase has aroused considerable interest as the major target for the discovery of anti-asthma agents, these differences at the binding site of AMCase may be exploited for selective inhibitor design. The binding affinities, deter- mined based on energy minimization studies, suggest a lower affinity of argadin for AMCase when compared to that for HCHT and AfchiB1. © 2010 Bentham Science Publishers Ltd.


Rathore R.S.,University of Hyderabad | Reddy R.N.,Rational Labs Pvt Ltd | Kondapi A.K.,University of Hyderabad | Reddanna P.,University of Hyderabad | And 2 more authors.
Theoretical Chemistry Accounts | Year: 2012

A quantum mechanics (QM)/molecular mechanics (MM)-based free energy perturbation (FEP) method, developed recently, provides most accurate estimation of binding affinities. The validity of the method was evaluated for a large set of diverse inhibitors for fructose 1,6-bisphosphatase (FBPase), a target enzyme for type-II diabetes mellitus. The validation set comprises of 22 important structurally different mutations. The calculated relative binding free energies using the QM/MM-based FEP method reproduce the experimental values with exceptional precision of less than ±0.5 kcal/mol. The CPU requirements for QM/MM-based FEP are about fivefold greater than conventional FEP methods, but it is superior in accuracy of predictions. In addition, the QM/MM-based FEP method eliminates the need for time-consuming development of MM force field parameters, which are frequently required for novel inhibitors described by MM. Future automation of the method and parallelization of the code for 128/256/512 cluster computers is expected to enhance the speed and increase its use for drug design and lead optimization. The present application of QM/MM-based FEP method for structurally diverse set of analogs serves to enhance the scope of FEP method and demonstrate the utility of QM/MM-based FEP method for its potential in drug discovery. © 2012 Springer-Verlag.


PubMed | Rational Labs Pvt Ltd
Type: Journal Article | Journal: Current pharmaceutical design | Year: 2013

Multiple approaches have been devised and evaluated to computationally estimate binding free energies. Results using a recently developed Quantum Mechanics (QM)/Molecular Mechanics (MM) based Free Energy Perturbation (FEP) method suggest that this method has the potential to provide the most accurate estimation of binding affinities to date. The method treats ligands/inhibitors using QM while using MM for the rest of the system. The method has been applied and validated for a structurally diverse set of fructose 1,6- bisphosphatase (FBPase) inhibitors suggesting that the approach has the potential to be used as an integral part of drug discovery for both lead identification lead optimization, where there is a structure available. In addition, this QM/MM-based FEP method was shown to accurately replicate the anomalous hydration behavior exhibited by simple amines and amides suggesting that the method may also prove useful in predicting physical properties of molecules. While the method is about 5-fold more computationally demanding than conventional FEP, it has the potential to be less demanding on the end user since it avoids development of MM force field parameters for novel ligands and thereby eliminates this time-consuming step that often contributes significantly to the inaccuracy of binding affinity predictions using conventional FEP methods. The QM/MM-based FEP method has been extensively tested with respect to important considerations such as the length of the simulation required to obtain satisfactory convergence in the calculated relative solvation and binding free energies for both small and large structural changes between ligands. Future automation of the method and parallelization of the code is expected to enhance the speed and increase its use for drug design and lead optimization.

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