Mayuso Kuno

Binding energy analysis for wild-type and Y181C mutant HIV-1 RT/8-Cl TIBO complex structures: Quantum chemical calculations based on the ONIOM method

Two‐layered and three‐layered ONIOM calculations were performed to compare the binding energies of 8‐Cl TIBO inhibitor when bound into the human immunodeficiency virus reverse transcriptase binding pocket and a Y181C variant. Both consisted of 20 residues within a radius of 15 Å. A combination of different methods [MP2/6‐31G(d), B3LYP/6‐31G(d,p), and PM3] were performed to take advantage of ONIOMs layering strategy analysis. The obtained results clearly indicate that the Y181C mutation reduces the binding affinity and stability of the inhibitor by approximately 8–9 kcal/mol as obtained from different combined MO:MO methods. Analyses regarding the energetic components of the interaction and deformation energies for 8‐Cl TIBO inhibitor upon binding were also examined extensively. Additional calculations involving the interaction energies between 8‐Cl TIBO with individual residues surrounding the binding pocket were performed at MP2/6‐31G(d,p) and B3LYP/6‐31G(d,p) levels of theory to gain more insight into the energetic differences of wild‐type and Y181C mutant type at the atomistic level. Proteins 2005.

Interaction evaluation of silver and dithizone complexes using DFT calculations and NMR analysis

Silver has distinct antibacterial properties and has been used as a component of commercial products with many applications. An increasing number of commercial products cause risks of silver effects for human and environment such as the symptoms of Argyria and the release of silver to the environment. Therefore, the detection of silver in the aquatic environment is important. The colorimetric chemosensor is designed by the basic of ligand interactions with metal ion, leading to the change of signals for the naked-eyes which is very useful method to this application. Dithizone ligand is considered as one of the effective chelating reagents for metal ions due to its high selectivity and sensitivity of a photochromic reaction for silver as well as the linear backbone of dithizone affords the rotation of various isomeric forms. The present study is focused on the conformation and interaction of dithizone with silver using density functional theory (DFT). The interaction parameters were determined in term of binding energy of complexes and the geometry optimization, frequency of the structures and calculation of binding energies using density functional approaches B3LYP and the 6-31G(d,p) basis set. Moreover, the interaction of silver-dithizone complexes was supported by UV-Vis spectroscopy, FT-IR spectrum that were simulated by using B3LYP/6-31G(d,p) and (1)H NMR spectra calculation using B3LYP/6-311+G(2d,p) method compared with the experimental data. The results showed the ion exchange interaction between hydrogen of dithizone and silver atom with minimized binding energies of silver-dithizone interaction. Therefore, the results can be the useful information for determination of complex interaction using the analysis of computer simulations.

Key interactions of the mutant HIV-1 reverse transcriptase/efavirenz: an evidence obtained from ONIOM method

Two-layered ONIOM calculations were performed in order to compare the binding of efavirenz (EFV) to the HIV-1 RT binding pocket of both wild type (WT) and K103N enzymes. The K103N mutation reduces the binding affinity of the inhibitor by 5.81 kcal mol−1 as obtained from the ONIOM2 (B3LYP/6-31G(d,p):PM3) method. These indicate that the loss of binding energy to K103N mutation can attribute to a weakened attractive interaction between the drug and residues surrounding in the binding pocket. The deformation of the K103N binding pocket requires more energy for structural rearrangement than that of the WT by approximately 4.0 kcal mol¬1. Moreover, the pairwise energies perfectly demonstrate that the K103N mutation affects on the loss of the interaction energy. In addition, the main influences are due to residues surrounding in the binding pocket; K101, K102, S105, V179, W229, P236 and E138. In particular, two residues; K101 and S105, established hydrogen bondings with the inhibitor. ONIOM calculations, resulting in the details of binding energy, interaction energy and deformation energy can be used to identify the key interaction and structural requirements of more potent HIV-1 RT inhibitor.

Photochemistry and mechanism of designed pyrenyl probe towards promoted cleavage of proteins

A new photochemical reagent, succinic acid-1(1-pyrene)methylamide (PMA-SUC), was developed to recognize the specific binding sites on model proteins, egg-white lysozyme and avidin. The interaction of the photochemical reagent with the proteins was studied by UV-Vis, fluorescence spectroscopic methods and docking description. PMA-SUC was found to bind to lysozyme and avidin with binding constants (Kb) of 2.4×105 and 6.7×105 (M-1), respectively. The fluorescence intensity of PMA-SUC decreased with increasing concentration of both proteins. Quenching of PMA-SUC fluorescence, in the absence and presence of the protein by an electron acceptor (Hexaamminecobalt(III) chloride, Co(NH3)6Cl3) showed no significant changes in the Ksv values (Stern-Volmer quenching constant), indicating that PMA-SUC bound to the hydrophilic sites or near the surface of the proteins. Irradiation of protein-PMA-SUC mixture, at 342nm for a period of time, in the presence of Co(NH3)6Cl3 as an electron acceptor, resulted in the cleavage of both proteins with high specificity. Binding mechanisms were studied using Molecular docking method. Molecular docking study indicated the position of PMA-SUC upon binding to the proteins by hydrogen bonding interaction with donor-acceptor within the distance of less than 5Å in the minimum of binding free energy. The docking results have supported the results obtained from the spectroscopic methods and cleavage studies.

Specific and Structural Study of Cu(II), Na(I) and CuNPs on PicolinicAcid Ligand

Extended Abstract Nanotechnology is rapidly growing form of modern technology, which have been widely researched and the development of a drug [1-2]. Picolinic acid is interesting to the pharmaceutical industry because of interaction with metal ions in the body [3-5]. Copper nanoparticles (Cu NPs) are also used in consumer products which humans can exposed in their bodies [6-7]. In this study, the interactions between picolinic acid with copper (II), sodium (I) and CuNPs were studied by using the B3LYP/6-31G (d,p) method. The structures, position of the O-O bond and N-O bond, the binding energy of the complex ratios of picolinic acid to metal ions of copper (II) or sodium (I) in the ratio of 1 : 1 were investigated in this study. The result show that the picolinic acid and copper (II) at the position between N-O bond with the binding energy of -493.838 kcal/mol, which is found to be more stable than the position between O-O bond. However, the binding energy of picolinic acid and sodium (I) at the position between the O-O bond was estimated to be -155.501 kcal/mol and more stable than the position between N-O bonds due to the decreasing energy calculation. Therefore, copper (II) is more specific than sodium (I) with picolinic acid. In addition, the comparison specificity between picolinic with copper (II) and copper nanoparticles. The result show that the picolinic acid and copper nanoparticles at the position between N-O bond, found to be more stable than the position between O-O bonds with the binding energy of -5850.242 kcal/mol. Due to the fact that CuNPs are smaller than copper (II) and show the best specificity and ability to bind the picolinic acid.

Tuning the chain length of new pyrene derivatives for site-selective photocleavage of avidin

Rational design of photoreagents with systematic modifications of their structures can provide valuable information for a better understanding of the protein photocleavage mechanism by these reagents. Variation of the length of the linker connecting the photoactive moiety with the protein anchoring-group allowed us to investigate the control of the protein photocleavage site. A series of new photochemical reagents (PMA-1A, PMA-2A and PMA-3A) with increasing chain lengths is examined in the current study. Using avidin as a model system, we examined the interaction of these probes by UV-Vis, fluorescence spectroscopic methods, photocleavage and computational docking studies. Hypochromism of the absorption spectrum was observed for the binding of these new photochemical reagents with estimated binding constants (Kb) of 6.2 × 105, 6.7 × 105 and 4.6 × 105 M-1, respectively. No significant changes of Stern-Volmer quenching constant (Ksv) with Co(NH3)6Cl3 has been noted and the data indicated that the probes bind near the surface of the protein with sufficient exposure to the solvent. Photoexcitation of the probe-avidin complex, in the presence of Co(NH3)6Cl3, resulted in protein fragmentation, and the cleavage yield decreased with the increase in the linker length, and paralleled with the observed Ksv values. Amino acid sequencing of the photofragments indicated that avidin is cleaved between Thr77 and Val78, as a major cleavage site for all the three photoreagents. This site is proximate to the biotin binding site on avidin, and molecular docking studies indicated that the H-bonding interactions between the polar end-group of the photoreagents and hydrophilic amino acids of avidin were important in positioning the reagent on the protein. The major cleavage site, at residues 77-78, was within 5 Å of the pyrenyl moiety of the probe, and hence, molecular tuning of the linker provided a simple approach to position the photoreagent along the potential photocleavage site.

Biotransformation of β-Mangostin by an Endophytic Fungus of Garcinia mangostana to Furnish Xanthenes with an Unprecedented Heterocyclic Skeleton

Biotransformation of β-mangostin (1) by the endophytic fungus Xylaria feejeensis GM06 afforded hexacyclic ring-fused xanthenes with an unprecedented hexacyclic heterocylic skeleton. β-Mangostin (1) was transformed to two diastereomeric pairs of enantiomers, mangostafeejin A [(-)-2a/(+)-2b)] and mangostafeejin B [(-)-3a/(+)-3b)]. The chemical structures of the transformation products were elucidated by analysis of NMR and MS data, and the structure of mangostafeejin A [(-)-2a/(+)-2b)] was confirmed by single-crystal X-ray diffraction analysis. The absolute configurations of 3a and 3b were established on the basis of calculated and measured ECD data using the ECD spectra of 2a and 2b as models. The fungal biotransformation described herein provides an effective method to convert an abundant achiral plant natural product scaffold into new chiral heterocyclic scaffolds representing expanded chemical diversity for biological activity screening.