Probable Binding Site Research Articles

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups.

The 14-3-3 protein family, one of the first discovered phosphoserine/phosphothreonine binding proteins, has attracted interest not only because of its important role in the cell regulatory processes but also due to its enormous number of interactions with other proteins. Here, we use a computational approach to predict the binding sites of the designed hybrid compound featuring aggregation-induced emission luminophores as a potential supramolecular ligand for 14-3-3ζ in the presence and absence of C-Raf peptides. Our results suggest that the area above and below the central pore of the dimeric 14-3-3ζ protein is the most probable binding site for the ligand. Moreover, we predict that the position of the ligand is sensitive to the presence of phosphorylated C-Raf peptides. With a series of experiments, we confirmed the computational prediction of two C2 related, dominating binding sites on 14-3-3ζ that may bind to two of the supramolecular ligand molecules.

Structural and Functional Analysis of Toxin and Small RNA Gene Promoter Regions in Bacillus anthracis.

It was previously demonstrated that anthrax toxin activator (AtxA) binds directly to the σA-like promoter region of pagA (encoding protective antigen, PA) immediately upstream of the RNA polymerase binding site. In this study, using electrophoretic mobility shift assays and in vivo analyses, we identified AtxA-binding sites in the promoter regions of the lef and cya genes (encoding lethal and edema factors, respectively) and of two Bacillus anthracis small RNAs (XrrA and XrrB). Activities of all four newly studied promoters were enhanced in the presence of CO2/bicarbonate and AtxA, as previously seen for the pagA promoter. Notably, the cya promoter was less activated by AtxA and CO2/bicarbonate conditions. The putative promoter of a recently described third small RNA, XrrC, showed a negligible response to AtxA and CO2/bicarbonate. RNA polymerase binding sites of the newly studied promoters show no consensus and differ from the σA-like promoter region of pagA. In silico analysis of the probable AtxA binding sites in the studied promoters revealed several palindromes. All the analyzed palindromes showed very little overlap with the σA-like pagA promoter. It remains unclear as to how AtxA and DNA-dependent RNA-polymerase identify such diverse DNA-sequences and differentially regulate promoter activation of the studied genes. IMPORTANCE Anthrax toxin activator (AtxA) is the major virulence regulator of Bacillus anthracis, the causative agent of anthrax. Understanding AtxA's mechanism of regulation could facilitate the development of therapeutics for B. anthracis infection. We provide evidence that AtxA binds to the promoters of the cya, lef, xrrA, and xrrB genes. In vivo assays confirmed the activities of all four promoters were enhanced in the presence of AtxA and CO2/bicarbonate, as previously seen for the pagA promoter. The cya and lef genes encode important toxin components. The xrrA and xrrB genes encode sRNAs with a suggested function as cell physiology regulators. Our data provides further evidence for the direct regulatory role of AtxA that was previously shown with the pagA promoter.

Homology Modeling and Molecular Docking Approaches for the Proposal of Novel Insecticides against the African Malaria Mosquito (Anopheles gambiae).

Vector-borne infectious diseases are responsible for the deaths of over 700,000 people annually, than 400,000 of them resulting from malaria. The mosquito Anopheles gambiae is one of the dominant vector species of human malaria transmission. A significant issue of the conventional insecticides which target the arthropod borne infectious diseases is their induced resistance. To overcome this inconvenience, insecticides with new modes of action are required. One of the most promising targets for the development of new potential insecticides as evidenced by current studies is the D1-like dopamine receptor (DAR). To get a deeper understanding of the structural information of this receptor, the 3D homology model was built. The possible sites within the protein were identified and the most probable binding site was highlighted. The homology model along with a series of DAR antagonists with known activity against Anopheles gambiae larvae were used in docking experiments to gain insight into their intermolecular interactions. Furthermore, virtual screening of the natural compounds from the SPECS database led to the prediction of toxicity and environmental hazards for one potential new insecticide against the Anopheles gambiae mosquito.

Synthesis, structural elucidation, biological screening, and density functional theory calculations of Cu(II), Ni(II), Mn(II), and Co(II) complexes of 20 Z‐N‐((Z)‐2‐(6‐nitrobenzo[d]thiazol‐2‐ylimino)‐1,2‐diphenylethylidene)‐5‐nitrobenzo[d]thiazol‐2‐amine Schiff base ligand

The emerging Schiff base‐derived metal complexes are the building blocks for biomedical applications. Herein, novel Schiff base N,N′‐[(1Z,2Z)‐1,2‐diphenylethane‐1,2‐diylidene]bis(6‐nitro‐1,3‐thiazol‐2‐amine) and corresponding Cu(II), Ni(II), Mn(II), and Co(II) metal complexes were successfully synthesized and characterized. The characterization of ligand and corresponding metal complexes was carried out by employing elemental analysis, 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy, Fourier transform infrared spectroscopy (FTIR) analysis, molar conductance, magnetic susceptibility measurements, electronic spectra, electronic paramagnetic resonance (EPR) and density functional theory (DFT) studies. DFT calculations at B3LYP/6‐311+G** level of theory have been executed to examine the equilibrium geometry of the ligand and metal complexes. Furthermore, total energy, highest‐occupied molecular orbital (HOMO) and lowest‐unoccupied molecular orbital (LUMO), and Mulliken atomic charges were reckoned. Tetrahedral geometry was observed in the case of the Ni(II) complex, and octahedral geometries were discerned for Cu(II), Mn(II), and Co(II), complexes. Docking studies were performed against the newly synthesized analogs with the active site of Escherichia coli (PDB ID: 3t88), Staphylococcus aureus (PDB ID: 3q8u), Candida Albicans (PDB ID: 3qlw), and Aspergillus flavus (PDB ID: 4ynt) receptors to recognize the interactions between complexes and identify their probable binding sites. Synthesized analogs were examined for in vitro antimicrobial activity employing both minimum inhibitory concentration and disk diffusion method against the aforementioned pathogens. The result for these pathogens suggested metal compounds evince higher activity in comparison to the free ligand.

Investigating a putative transcriptional regulatory protein encoded by Rv1719 gene of Mycobacterium tuberculosis.

Mycobacterium tuberculosis, the causative agent of tuberculosis, demonstrates immense plasticity with which it adapts to a highly dynamic and hostile host environment. This is facilitated by a web of signalling pathways constantly modulated by a multitude of proteins that regulate the flow of genetic information inside the pathogen. Transcription factors (TFs) belongs to one such family of proteins that modulate the signalling by regulating the abundance of proteins at the transcript level. In the current study, we have characterized the putative transcriptional regulatory protein encoded by the Rv1719 gene of Mycobacterium tuberculosis. This TF belongs to the IclR family of proteins with orthologs found in both bacterial and archaeal species. We cloned the Rv1719 gene into the pET28a expression vector and performed heterologous expression of the recombinant protein with E coli as the host. Further, optimization of the purification protocol by affinity chromatography and characterization of proteins for their functional viability has been demonstrated using various biochemical and/or biophysical approaches. Scale-up of purification yielded approximately 30mg of ~ 28kDa protein per litre of culture. In-silico protein domain analysis of Rv1719 protein predicted the presence of the helix-turn-helix (HTH) domain suggesting its ability to bind DNA sequence and modulate transcription; a hallmark of a transcriptional regulatory protein. Further, by performing electrophoretic mobility shift assay (EMSA) we demonstrated that the protein binds to a specific DNA fragment harboring the probable binding site of one of the predicted promoters.

Supramolecular Arrangement and DFT analysis of Zinc(II) Schiff Bases: An Insight towards the Influence of Compartmental Ligands on Binding Interaction with Protein.

We report, for the first time, a detailed crystallographic study of the supramolecular arrangement for a set of zinc(II) Schiff base complexes containing the ligand 2,6‐bis((E)‐((2‐(dimethylamino)ethyl)imino)methyl)‐4‐R‐phenol], where R=methyl/tert‐butyl/chloro. The supramolecular study acts as a pre‐screening tool for selecting the compartmental ligand R of the Schiff base for effective binding with a targeted protein, bovine serum albumin (BSA). The most stable hexagonal arrangement of the complex [Zn−Me] (R=Me) stabilises the ligand with the highest FMO energy gap (ΔE=4.22 eV) and lowest number of conformations during binding with BSA. In contrast, formation of unstable 3D columnar vertebra for [Zn−Cl] (R=Cl) tend to activate the system with lowest FMO gap (3.75 eV) with highest spontaneity factor in molecular docking. Molecular docking analyses reported in terms of 2D LigPlot+ identified site A, a cleft of domains IB, IIIA and IIIB, as the most probable protein binding site of BSA. Arg144, Glu424, Ser428, Ile455 and Lys114 form the most probable interactions irrespective of the type of compartmental ligands R of the Schiff base whereas Arg185, Glu519, His145, Ile522 act as the differentiating residues with ΔG=−7.3 kcal mol−1.

Elucidating the Role of the Hsc70 Chaperone System in SNARE Complex Formation

Neurons communicate through neurotransmitters that are released into the synaptic cleft. For this release to occur a synaptic vesicle must fuse with the plasma membrane in the presynaptic terminal of neurons. Fusion requires the formation of the SNARE complex, which is composed of four helices from three proteins: one helix from syntaxin, one helix from synaptobrevin, and two from SNAP‐25 (one from the C‐terminal and one from the N‐terminal). This fusion process is tightly regulated and requires an Hsp70 chaperone system including the constitutive cytoplasmic Hsp70, Hsc70, and its co‐chaperones CSPɑ (a J protein) and Hsp110 (a nucleotide‐exchange factor). However, the molecular details of this system are still poorly understood. SNAP‐25 is a disordered protein that is prone to aggregation and premature folding. Therefore, we hypothesize that SNAP‐25 is chaperoned by Hsc70 to ensure that it remains in a state that is competent for SNARE complex formation. Using a peptide array of SNAP‐25, we identified three most probable binding sites of Hsc70 on SNAP‐25. We took the advantage of the fact that the fully formed SNARE complex is SDS‐resistant and used SDS‐PAGE to monitor successful reconstitution of the SNARE complex in vitro. Our preliminary data support our hypothesis in that the addition to Hsc70 facilitates the formation of the SNARE complex. Our goal is to elucidate in detail the molecular interactions of Hsc70 and CSPɑ with the SNARE complex components, notably SNAP‐25, in the formation of the SNARE complex and the initial stages of synaptic vesicle fusion.

Biophysical and molecular modeling evidences for the binding of sulfa molecules with hemoglobin

The molecular mechanism of the heme protein, hemoglobin (Hb) interaction with sulfa molecule, sulfadiazine (SDZ) has been investigated through spectroscopic, neutron scattering and molecular modeling techniques. Absorption and emission spectroscopic studies showed that SDZ molecules were bound to Hb protein, non-cooperatively. The binding affinityof SDZ-Hb complex at standard experimental condition was evaluated to be around (4.2 ± 0.07) ×104, M−1with 1:1 stoichiometry. Drug induced structural perturbation of the 3 D protein moiety was confirmed through circular dichroism (CD), synchronous fluorescence and small angle neutron scattering methods. From the temperature dependent spectrofluorometric studies, the negative standard molar Gibbs energy change suggested the spontaneity of the reaction. The negative enthalpy and positive entropy change(s) indicated towards the involvement of both electrostatic and hydrophobic forces during the association process. Salt dependent fluorescence study revealed major contributions from non-poly-electrolytic forces. Molecular modeling studies determined the probable binding sites, types of interaction involved and the conformational alteration of the compactness of the Hb structure upon interaction with SDZ molecule. Overall, the study provides detailed insights into the binding mechanism of SDZ antibiotics to Hb protein. Communicated by Ramaswamy H. Sarma

Heme Protein Binding of Sulfonamide Compounds: A Correlation Study by Spectroscopic, Calorimetric, and Computational Methods.

Protein–ligand interaction studies are useful to determine the molecular mechanism of the binding phenomenon, leading to the establishment of the structure–function relationship. Here, we report the binding of well-known antibiotic sulfonamide drugs (sulfamethazine, SMZ; and sulfadiazine, SDZ) with heme protein myoglobin (Mb) using spectroscopic, calorimetric, ζ potential, and computational methods. Formation of a 1:1 complex between the ligand and Mb through well-defined equilibrium was observed. The binding constants obtained between Mb and SMZ/SDZ drugs were on the order of 104 M–1. SMZ with two additional methyl (−CH3) substitutions has higher affinity than SDZ. Upon drug binding, a notable loss in the helicity (via circular dichroism) and perturbation of the three-dimensional (3D) protein structure (via infrared and synchronous fluorescence experiments) were observed. The binding also indicated the dominance of non-polyelectrolytic forces between the amino acid residues of the protein and the drugs. The ligand–protein binding distance signified high probability of energy transfer between them. Destabilization of the protein structure upon binding was evident from differential scanning calorimetry results and ζ potential analyses. Molecular docking presented the best probable binding sites of the drugs inside protein pockets. Thus, the present study explores the potential binding characteristics of two sulfonamide drugs (with different substitutions) with myoglobin, correlating the structural and energetic aspects.

Theoretical Study of the Structural Stability, Chemical Reactivity, and Protein Interaction for NMP Compounds as Modulators of the Endocannabinoid System.

The cannabinoid receptors (CB1/CB2) and the T-type calcium channels are involved in disorders associated with both physiological pain and depressive behaviors. Valuable pharmacological species carbazole derivatives such as the NMP-4, NMP-7, and NMP-181 (Neuro Molecular Production) regulate both biological entities. In this work, DFT calculations were performed to characterize theoretically their structural and chemical reactivity properties using the BP86/cc-pVTZ level of theory. The molecular orbital contributions and the chemical reactivity analysis reveal that a major participation of the carbazole group is in the donor-acceptor interactions of the NMP compounds. The DFT analysis on the NMP compounds provides insights into the relevant functional groups involved during the ligand-receptor interactions. Molecular docking analysis is used to reveal possible sites of interaction of the NMP compounds with the Cav3.2 calcium channel. The interaction energy values and reported experimental evidence indicate that the site denominated as “Pore-blocking”, which is formed mainly by hydrophobic residues and the T586 residue, is a probable binding site for the NMP compounds.

Design, Synthesis, Theoretical, Spectroscopic and Molecular Docking Studies of Ruthenium and Zinc Complexes and their Antimycobacterial Study

The six mononuclear complexes of ruthenium and zinc viz. [Ru(bpy)2(HL1)]Cl (ML1), [Ru(bpy)2(HL2)]Cl (ML2), [Ru(bpy)2(HL3)]Cl (ML3), [ZnCl(H2O)HL1]Cl (ML4), [ZnCl(H2O)HL2]Cl (ML5), [ZnCl(H2O)HL3]Cl (ML6); bpy = 2,2′-bipyridyl, HL = substituted thiosemicarbazone: HL1 = Cl, HL2 = OCH3, HL3 = OCH2Ph) were synthesized and characterized by elemental analysis, IR, 1H and 13C NMR, UV-Vis and ESI-MS spectroscopy techniques. The gas phase geometries of all the complexes have been optimized by density functional theory (DFT). The antimycobacterial activity of all the compounds was performed initially at 100 μM concentration, followed by MIC determination studies with compounds, which showed 90% reduction in fluorescence intensity. In addition, molecular docking analysis was performed to know the interactions between complexes and their probable binding sites in penicillin binding protein (PBP2). The 90% reduction in fluorescence intensity of the mycobacterial cultures were observed with HL2, HL3 and ML3. The MIC determination study showed good inhibition of ML3 and HL3 treated cultures even at 25 μM concentration. The potential activity shown by HL3 and ML3 cultures shows to be promising compounds, which may be further optimized for improved antimycobacterial activity. Electronic properties and various reactivity descriptors have been determined theoretically and an attempt has been perform to establish the correlation between biological activity and these parameters for the concerned metal complexes.

Design, Synthesis and Pharmacological Assay of Sulfadiazine based Azo-Metal Complexes

This study reported the biologically active Cu(II), Co(II) and Ni(II) complexes of the novel azo dye ligand pyrimidin-2-yl-4-[(E)-(2,4,6-trioxohexahydropyrimidin-5-yl)diazenyl]benzenesulfonamide. The structures of synthesized metal complexes were established on spectroscopic and physico-chemical techniques. From the spectral studies, it confirms that the azo ligand coordinates to the metal center through a bidendate manner via barbutaric acid -OH, azo-N as a donor site. The thermal studies reveals that all the complexes exhibits good thermally stability and also the presence of water molecule for Co(II) and Ni(II) complexes. The prepared metal chelates have been examined for their antibacterial activity against Staphylococcus aureus, Xanthomonas campestris, Klebsiella pneumonia and E. coli by using agar well diffusion method. The data revealed the ability of the complexes to inhibit the growth of some microorganisms, among all the compounds Co(II) complex showed the highest activity. The antifungal activity of the compounds were tested against two strains, whereas Ni(II) complex showed the highest activity against fungal strains. Lastly, the probable binding sites of metal complexes with receptor RpsA were studied by molecular docking studies.

Albumin-Hyaluronan Interactions: Influence of Ionic Composition Probed by Molecular Dynamics.

The lubrication mechanism in synovial fluid and joints is not yet fully understood. Nevertheless, intermolecular interactions between various neutral and ionic species including large macromolecular systems and simple inorganic ions are the key to understanding the excellent lubrication performance. An important tool for characterizing the intermolecular forces and their structural consequences is molecular dynamics. Albumin is one of the major components in synovial fluid. Its electrostatic properties, including the ability to form molecular complexes, are closely related to pH, solvation, and the presence of ions. In the context of synovial fluid, it is relevant to describe the possible interactions between albumin and hyaluronate, taking into account solution composition effects. In this study, the influence of Na+, Mg2+, and Ca2+ ions on human serum albumin–hyaluronan interactions were examined using molecular dynamics tools. It was established that the presence of divalent cations, and especially Ca2+, contributes mostly to the increase of the affinity between hyaluronan and albumin, which is associated with charge compensation in negatively charged hyaluronan and albumin. Furthermore, the most probable binding sites were structurally and energetically characterized. The indicated moieties exhibit a locally positive charge which enables hyaluronate binding (direct and water mediated).

Spectroscopic Investigation of Electron-Releasing Functional Groups Substituted N-Iso-Butyl, S-2-Nitro-1-Phenylethyl Dithiocarbamate – A DFT Approach

Quantum chemical calculations have been carried out to explore structural and spectroscopic properties of some derivatives of N-iso-butyl, S-2-nitro-1-phenylethyl dithiocarbamate molecule in neutral and cationic forms. Electron-releasing groups (Me, OH and OMe) are considered to explore their effect on geometrical parameters, vibrational spectra and electronic properties of N-iso-butyl, S-2-nitro-1-phenylethyl dithiocarbamate. All the computations were performed at DFT/B3LYP level of Gaussian09 suite. The Raman spectra at different laser exciting frequencies are presented. The potential energy distributions of the considered derivatives were calculated by using the normal coordinate analysis method. The NBO calculations were performed to study the donor-acceptor interactions, HOMO-LUMO, electronic structure and hyper-conjugative interaction energies. The vibrational contribution of various thermodynamical parameters, viz, entropy, specific heat and free energy have also been presented and discussed in detail. Moreover, we have also explored the effect of temperature at specific heat and partition function of these molecules. Molecular docking studies have been performed to understand the nature of the interactions and the probable binding sites of NSD, NSD-Me, NSD-OH and NSD-OMe molecules in the active pockets of the 2KCE receptor.

Evaluation of potassium ferrate activated biochar for the simultaneous adsorption of copper and sulfadiazine: Competitive versus synergistic

Combined pollution caused by organic pollutants and heavy metals pose a significant challenge to the adsorption process. In this study, iron-modified biochar (Fe-BC) was prepared by using ferrate (K2FeO4) and wheat stalk as the precursors for the adsorption of copper (Cu2+) and sulfadiazine (SDZ), especially under combined pollution scenarios. Iron modification not only enlarged the surface area but also loaded iron oxide nanoparticles on biochar surface. Accordingly, Fe-BC exhibited better adsorption capability of Cu2+ and SDZ than the pristine biochar (BC). The corresponding maximum adsorption capacities of Fe-BC700 were 46.85 mg g−1 and 45.43 mg g−1 towards Cu2+ and SDZ, respectively. Interestingly, the adsorption was elevated in binary-pollutants system, suggesting a synergistic effect, which was probably attributed to the mutual bridging effects and complexation between Cu2+ and SDZ. The loaded iron oxide particles could serve as a physical barrier to separate the adsorptions of Cu2+ and SDZ and thus inhibited the competitive adsorption. Meanwhile, theoretical calculation demonstrated that sulfonamide group was the most probable binding site. Columns packed with Fe-BC700 showed better performances for Cu2+ and SDZ removal in binary system (635.73 BV for Cu2+ and 4846.26 BV for SDZ) than in single systems (571.60 BV for Cu2+ and 3572.06 BV for SDZ), which was consistent with batch adsorption experiments. These results demonstrated the potential application of Fe-BC700 for simultaneous adsorption of Cu2+ and SDZ and provided a cost-effective way for the remediation of organic and inorganic pollutants.

Finding potential inhibitors against RNA-dependent RNA polymerase (RdRp) of bovine ephemeral fever virus (BEFV): an in-silico study

The bovine ephemeral fever virus (BEFV) is an enzootic agent that affects millions of bovines and causes major economic losses. Though the virus is seasonally reported with a very high morbidity rate (80–100%) from African, Australian, and Asiatic continents, it remains a neglected pathogen in many of its endemic areas, with no proper therapeutic drugs or vaccines presently available for treatment. The RNA-dependent RNA polymerase (RdRp) catalyzes the viral RNA synthesis and is an appropriate candidate for antiviral drug developments. We utilized integrated computational tools to build the 3D model of BEFV-RdRp and then predicted its probable active binding sites. The virtual screening and optimization against these active sites, using several small-molecule inhibitors from a different category of Life Chemical database and FDA-approved drugs from the ZINC database, was performed. We found nine molecules that have docking scores varying between −6.84 to −10.43 kcal/mol. Furthermore, these complexes were analyzed for their conformational dynamics and thermodynamic stability using molecular dynamics simulations in conjunction with the molecular mechanics generalized Born surface area (MM-GBSA) scheme. The binding free energy calculations depict that the electrostatic interactions play a dominant role in the RdRp-inhibitor binding. The hot spot residues, such as Arg565, Asp631, Glu633, Asp740, and Glu707, were found to control the RdRp-inhibitor interaction. The ADMET analysis strongly suggests favorable pharmacokinetics of these compounds that may prove useful for treating the BEFV ailment. Overall, we anticipate that these findings would help explore and develop a wide range of anti-BEFV therapy. Communicated by Ramaswamy H. Sarma

Molecular insight on the binding of stevia glycosides to bovine serum albumin

The interaction of the steviol and its glycosides (SG), steviolbioside, and rebaudioside A, with bovine serum albumin (BSA) was studied by absorption and fluorescence spectroscopy techniques alongside molecular docking. The stevia derivatives quenched the fluorescence of BSA by a dynamic quenching mechanism, indicating the interaction between the stevia derivatives and BSA. The binding constant (Kb) of steviol was 100-1000-fold higher than those of SG. The stevia derivative/BSA binding reaction was spontaneous and involved the formation of hydrogen bonds and van der Waals interactions between steviol and steviolbioside with BSA, and water reorganization around the rebaudioside A/BSA complex. Molecular docking pointed out the FA1 and FA9 binding sites of BSA as the probable binding sites of steviol and SG, respectively. In conclusion, steviol enhanced hydrophobicity and small size compared to SG may favor its binding to BSA. As steviol and its glycosides share binding sites on BSA with free fatty acids and drugs, they may be competitively displaced from plasma albumin under various physiological states or disease conditions. These findings are clinically relevant and provide an insight into the pharmacokinetics and pharmacodynamics of the stevia glycosides.

Multi technique investigation on interaction between 5-(2-thiazolylazo)-2,4,6-triaminopyrimidine and HSA and BSA

In research laboratories and in various industries, azo compounds are among the most effective and commonly used organic dyes. The association between human (HSA) and bovine (BSA) serum albumins with 5-(2-thiazolylazo)-2,4,6-triaminopyrimidine (TTP) was investigated in this research using spectroscopy methods and molecular modeling study. The fluorescence quenching results showed that the quenching mechanisms were static and dynamic processes for HSA and BSA, respectively. From the thermodynamic observations, it is clear that the binding process is a spontaneous molecular interaction, in which van der Waals and hydrogen bonding interactions for HSA and hydrophobic interaction for BSA play the major roles. According to Förster energy transfer, non-radiative energy transferred from HSA and BSA to TTP, is provided by close distance (r 0) between TTP and Trp residues of HSA and BSA. The synchronous fluorescence spectroscopy, FT-IR findings and UV-Vis absorption data confirm that TTP can induce conformational and micro environmental changes in both the proteins. Furthermore, docking results predicted the probable binding site of TTP in subdomain IIA of HSA and BSA molecules where Trp residues are located. Types of amino acid residues surrounding the TTP molecule supported that van der Waals forces, hydrophobic forces and electrostatic forces play important roles in stabilization of drug-protein complexes formed. Communicated by Ramaswamy H. Sarma

Mixed-ligand complexes of ampicillin derived Schiff base ligand and Nicotinamide: Synthesis, physico-chemical studies, DFT calculation, antibacterial study and molecular docking analysis

A novel series of mixed-ligand complexes of the type, [ML1(L2)3]Clx [M= Cr(III), Fe(III), Co(II),Ni(II), Cu(II), Cd(II) and Hg(II), n = 2, 3], was synthesized using Schiff base (HL1) as main ligand, nicotinamide (L2) as secondary ligand, and the corresponding metal ions in 1:3:1 molar ratio. The main ligand, HL1 was prepared by the interaction of ampicillin drug and 4-chlorobenzophenone. The synthesized mixed ligand complexes were characterized by elemental analysis, UV-Vis, FT-IR,1H-NMR,13C-NMR and TG/DTG studies. In the mixed-ligand complexes, the Schiff base ligand, HL1 showed coordination to the central metal ion in tridentate manner via azomethine nitrogen, β-lactam ring oxygen and deprotonated carboxylic oxygen atoms, whereas the secondary ligand L2 (nicotinamide, Nam) coordinated through pyridine nitrogen atoms. The synthesized complexes exhibited significant antimicrobial activity when evaluated against P. pseudomonas, E. coli, S. aureus and B. subtilis microbes. The DFT calculations were also carried out to ascertain the bonding insights into the structure. In addition, molecular docking analysis was performed carried out to know the interactions between complexes and their probable binding sites in penicillin binding protein (PBP2). Moreover, drug-likeness and toxicity of the compounds were also performed to predict the suitability of the complexes as drugs.

Computational and Experimental Study on the Interaction of Terbium(III) and Ytterbium(III) Complexes Containing 1,10-phenanthroline with Bovine Serum Albumin

In this work, the interaction of two synthesized complexes [Tb(phen)2Cl3.OH2] and [Yb(phen)2Cl3.OH2] (phen is 1,10-phenanthroline) with bovine serum albumin (BSA) were studied by UV-Vis, fluorescence, and molecular docking examinations. The experimental data indicated that these lanthanide complexes have a high binding affinity with BSA by effectively quenched the fluorescence of BSA via the static mechanism. The binding parameters, the type of interaction, the value of resonance energy transfer, and the binding distance between complexes and BSA were estimated from the analysis of fluorescence measurements and Forster theory. The thermodynamic parameters suggested that van der Waals interactions and hydrogen bonds play an important role in the binding mechanism. While the energy transfer from BSA molecules to these complexes occurs with high probability, the binding constants showed that the binding affinity ranked in the order Tb-complex > Yb-complex that has been related to the radius of Ln3+ ion. Also, the results of competitive experiments and molecular docking calculations assessed the microenvironment residues around the bound mentioned complexes and represent site 3 of BSA, located in subdomain IB, as the most probable binding site for these complexes. The computational results kept in good agreement with experimental data.