Conformational study of the structure of 18-thiacrown-6

Conformational analysis was performed for 18-thiacrown-6 (18t6) using the CONFLEX method and the MMFF94s force field. Computations were performed for some of the low energy conformations at the HF, B3LYP, CAM-B3LYP, M06, M06L, M062x, M06HF and MP2 levels. The computations were also performed using the DFT-D3 method along with the TPSS and PBE functionals. The study predicted a new C₂ conformation as the ground state conformation of 18t6. This new C₂ conformation is more stable than the experimentally known solid state conformation by 4.7 kcal/mol at the MP2/6-311G** level. This conformation has all of the SCCS dihedral angles adopt exodentate structure. However, the experimentally known conformation of the solid phase has two of the SCCS dihedral angles violating this exodentate rule. It was concluded that for 18t6 stability a linear dihedral SCCS angle requirement is more important than a gauche CSCC dihedral angle requirement.     

Stereoelectronic interaction effects on the conformational properties of hydrogen peroxide and its analogues containing S and Se atoms: An ab initio,hybrid-DFT study and NBO analysis

Ab initio molecular orbital (MP2/6-311+G**//MP2/6-31G+G**) and hybrid-density functional theory (B3LYP/6-311+G**//MP2/6-311+G**) methods and NBO analysis were used to study the stereoelectronic interaction effects on the conformational properties of hydrogen peroxide (1), hydrogen disulfide (2) and hydrogen diselenide (3). The results showed that the Gibbs free energy difference (G_T − G_S) values at 298.15 K and 1 atm between the skew (S) and trans (T) conformations (ΔG_T–S) increase from compound 1 to compound 2 but decrease from compound 2 to compound 3. The C conformations of compounds 1–3 are less stable than their S and T conformations. Based on these results, the racemization processes of the axial symmetrical (C₂ symmetry) conformations of compounds 1–3 take place via their T conformations. Based on the optimized ground state geometries using the MP2/6-311+G** level of theory, the NBO analysis of donor–acceptor (bond–antibond) interactions revealed that the stabilization (resonance) energy associated with LP₂M2 → σ*_M3-H4 electronic delocalization for the S conformations of compounds 1–3 are 1.35, 5.94 and 4.68 kcal mol⁻¹, respectively. There is excellent agreement between the variations of the calculated ΔG_T–S and stabilization (resonance) energies associated with LP₂M2→σ*_M3-H4 electronic delocalization for the S conformations of compounds 1–3. The correlations between resonance energies, orbital integrals, dipole moments, bond orders, structural parameters and conformational behaviors of compounds 1–3 have been investigated. Test were made of complete basis set methods (CBS-QB3, CBS-4 and CBS-Q), the first two gave results essentially indistinguishable from those we used, but the CBS-Q results were in disagreement with experimental and other theoretical results.     

An expert protein loop refinement protocol by molecular dynamics simulations with restraints

Protein structure prediction (PSP) is a long standing problem in structural biology and bioinformatics. Within the PSP problem loop refinement is a major bottleneck. In this article we report the latest version of the CReF expert predictor system for the PSP problem with emphasis on loop refinement of the approximate 3-D structure 1ZDD_P of the Z34C mini protein predicted by CReF. We designed a loop refinement protocol based on seven molecular dynamics (MD) simulations runs at different temperatures. We found that, by letting the loop residues move freely during dynamics at 325 K and restraining the internal coordinates of the correctly predicted helical structures, while allowing them to move relative to each other, the refinement protocol was very effective in predicting an accurate loop conformation in the first 100 ps of a 1000 ps MD simulation. The quality of the predictions was confirmed by the RMSD between refined and experimental structures which varied from 0.6 to 1.3 Å. In addition, stereochemical analyses showed that 100% of all residues of the refined 1ZDD_P, including those in the loop, populates the most favorable core regions of the Ramachandran plot. Our study suggests that the proposed protocol may be suitable to refine more complex mini proteins with different classes and architectures.     

The conformational behavior,geometry and energy parameters of Menshutkin-like reaction of O-isopropylidene-protected glycofuranoid mesylates in view of DFT calculations

The formation of pyridinium salts in the transformation of three O-isopropylidene-protected mesylates of furanoid sugar derivatives under pyridine action is considered at the B3LYP/6-31+G** computation level. All the structures were optimized in the gas phase, in chloroform and water. Activation barrier heights in the gas phase were also estimated at the B3LYP/6-311++G**, MPW1K/6-31+G** and MPW1K/6-311++G** levels. The conducted calculations, both in the gas phase (regardless of the computation level) and in solvents, revealed the barrier height increasing order as follows: 1 > 2 > 3 for the three reactions studied. The conformational behavior of the five-membered ring is discussed in the gas phase and in solvents. The fused dioxolane ring makes the furanoid ring less likely to undergo conformational changes. In the case of reaction 3, the furanoid ring shape does not change either in the gas phase or in solvents. All conformers are close to E₀ or ⁰E.     

Vibrational analysis and formation mechanism of typical deep eutectic solvents: An experimental and theoretical study

Deep eutectic solvents (DESs), as ionic liquid analogues for green solvents, have gained increasing attentions in chemistry. In this work, three typical kinds of DESs (ChCl/Gly, ChCl/AcOH and ChCl/Urea) were successfully synthesized and characterized by Fourier transform infrared spectroscopy (FTIR) and Raman. Then comprehensive and systematical analyses were performed by the methods of density functional theory (DFT). Two methods (B3LYP/6-311 + +G(2d,p) and dispersion-corrected B3LYP-D3/6-311 + +G(2d,p)) were employed to investigate the structures, vibrational frequencies and assign their ownership of vibrational modes for the DESs, respectively. Nearly all the experimental characteristic peaks of IR and Raman were identified according to the calculated results. By linear fitting of the combined calculated vs experimental vibration frequencies, it can be found that both of the two methods are excellent to reproduce the experimental results. Besides, hydrogen bonds were proved to exist in DESs by IR spectrum, structure analysis and RDG analysis. This work was aimed at predicting and understanding the vibrational spectra of the three typical DESs based on DFT methods. Moreover, by comparing experimental and theoretical results, it provides us a deep understanding of the formation mechanisms of DESs.     

A GMDH polynomial neural network-based method to predict approximate three-dimensional structures of polypeptides

Tertiary Protein Structure Prediction is one of the most important problems in Structural Bioinformatics. Along the last 20 years many algorithms have been proposed as to solve this problem. However, it still remains a challenging issue because of the complexity and of the dimensionality of the protein conformational search space. In this article a first principle method which uses database information for the prediction of the 3-D structure of polypeptides is presented. The technique is based on the Group Method of Data Handling (GMDH) algorithm, implemented by a software tool introduced on this work. GMDH Polynomial Neural Networks have been used with success in many fields such as data mining, knowledge discovery, pattern recognition and prediction. The proposed method was tested with seven protein sequences whose sizes vary from 14 to 54 amino acid residues. Results show that the predicted tertiary structures adopt a fold similar to the experimental structures. RMSD and secondary structure analysis reveal that the proposed method present accurate results in their predictions. The predicted structures can be used as input structures in refinement methods based on molecular mechanics (MM), e.g. molecular dynamics (MD) simulations. The search space is expected to be greatly reduced and the ab initio methods can demand a much reduced computational time to achieve a more accurate polypeptide structure.     

Tuning the push–pull configuration for efficient second-order nonlinear optical properties in some chalcone derivatives

Using the density functional theory methods, we effectively tune the second-order nonlinear optical (NLO) properties in some chalcone derivatives. Various unique push–pull configurations are used to efficiently enhance the intramolecular charge transfer process over the designed derivatives, which result in significantly larger amplitudes of the first hyperpolarizability as compared to their parent molecule. The ground state molecular geometries have been optimized using B3LYP/6-311G** level of theory. A variety of methods including B3LYP, CAM-B3LYP, PBE0, M06, BHandHLYP and MP2 are tested with 6-311G** basis set to calculate the first hyperpolarizability of parent system 1. The results of M06 are found closer to highly correlated MP2 method, which has been selected to calculate static and frequency dependent first hyperpolarizability amplitudes of all selected systems. At M06/6-311G** level of theory, the permanent electronic dipole moment (μ_tot), polarizability (α₀) and static first hyperpolarizability (β_tot) amplitudes for parent system 1 are found to be 5.139 Debye, 274 a. u. and 24.22 × 10⁻³⁰ esu, respectively. These amplitudes have been significantly enhanced in designed derivatives 2 and 3. More importantly, the (β_tot) amplitudes of systems 2 and 3 mount to 75.78 × 10⁻³⁰ and 128.51 × 10⁻³⁰ esu, respectively, which are about 3 times and 5 times larger than that of their parent system 1. Additionally, we have extended the structure-NLO property relationship to several newly synthesized chalcone derivatives. Interestingly, the amplitudes of dynamic frequency dependent hyperpolarizability μβ_ω (SHG) are also significantly larger having values of 366.72 × 10⁻⁴⁸, 856.32 × 10⁻⁴⁸ and 1913.46 × 10⁻⁴⁸ esu for systems 1–3, respectively, at 1400 nm of incident laser wavelength. The dispersion behavior over a wide range of change in wavelength has also been studied adopting a range of wavelength from 1907 to 544 nm. Thus, the present work realizes the potential of designed derivatives as efficient NLO-phores for modern NLO applications.     

The hydration structure of 18-crown-6/K+ complex as studied by Monte Carlo simulation using ab initio fitted potential

The intermolecular potential between a 18-crown-6/K+ complex and a water molecule is derived from 1200 energy points obtained from quantum chemical calculations using the 6-31G** basis set. The ab initio fitted potential was then applied to study the structural properties of the complex in an aqueous solution using the Monte Carlo simulation method. The radial distribution function (RDF) centered at K+ to the oxygen atom of water shows a sharp first peak at 2.88 A. The corresponding coordination number, integrated up to the first minimum at 3.76 A, is 2 water molecules. The results indicate clearly that the 18-crown-6/K+ complex was solvated by the two nearest neighbors, one above and other below the ligand's plane. Evaluation was focused on the precise position and orientation of the two water molecules. It was found that the oxygen atoms of the two nearest neighbors bind to the K+ while their hydrogen atoms rotate freely around the vector perpendicular to the ligand's molecular plane.     

Design of embedded TCAM based longest prefix match search engine

The content addressable memory (CAM) based solutions are very useful in network applications due to its high speed parallel search mechanism. This paper presents a novel Ternary CAM (TCAM) based NAND Pseudo CMOS–Longest Prefix Match (NPC–LPM) search engine. The proposed system provides a simple hardware based solution using novel 11T TCAM cell structures and NPC word line technique, for network routers. The experiments were performed on 256 × 128 NPC–LPM system under 0.13 μm technology. The simulation result shows that the proposed design provides low power dissipation of 5.78 mW and high search speed of 315 MSearches/s under 1.3 V supply voltage. The presented NPC–LPM system meets the speed requirement of Optical Carrier (OC) 3072 with line-rate of 160 Gb/s in Ethernet networking and IPv6 protocol. The experimental results also show that the proposed system improves power-performance by 65%.     

冠醚构象特征的分子力学分析

用分子力学程序ＭＭＰＭ对１２－冠－４、１２－氮冠－４、１２－硫冠－４、１８－冠－６、１８－氮冠－６、１８－硫冠－６的不同构象的能量进行了计算。结果表明,对于（－ＣＨ_２－ＣＨ_２－Ｘ－）_ｎ类的“冠醚”化合物,Ｘ＝Ｎ,Ｏ时,其低能构象中有最多的Ｘ－ＣＨ_２－ＣＨ_２－Ｘ旁式和最多的ＣＨ_２－Ｘ－ＣＨ_２－ＣＨ_２反式构象;Ｘ＝Ｓ时,情况与此相反。     

A comparative study of different local search application strategies in hybrid metaheuristics

This paper presents results of a comparative study with the objective to identify the most effective and efficient way of applying a local search method embedded in a hybrid algorithm. The hybrid metaheuristic employed in this study is called “DE–HS–HJ” because it is comprised of two cooperative metaheusitic algorithms, i.e., differential evolution (DE) and harmony search (HS), and one local search (LS) method, i.e., Hooke and Jeeves (HJ) direct search. Eighteen different ways of using HJ local search were implemented and all of them were evaluated with 19 problems, in terms of six performance indices, covering both accuracy and efficiency. Statistic analyses were conducted accordingly to determine the significance in performance differences. The test results show that overall the best three LS application strategies are applying local search to every generated solution with a specified probability and also to each newly updated solution (NUS + ESP), applying local search to every generated solution with a specified probability (ESP), and applying local search to every generated solution with probability and also to the updated current global best solution (EUGbest + ESP). ESP is found to be the best local search application strategy in terms of success rate. Integrating it with NUS further improve the overall performance. EUGbest + ESP is the most efficient and it is also able to achieve high level of accuracy (the fourth place in terms of success rate with an average above 0.9).     

Two novel proposed discrete wavelet transform and filter based approaches for short-circuit faults detection in power transmission lines

In this study, two approaches are presented to detect short-circuit faults in power transmission lines. The two proposed methods are completely novel from both theoretical and technical aspects. The first approach is a soft computing method that uses discrete wavelet transform with Daubechies mother wavelets db1, db2, db3, and db4. The second approach is a hardware based method that utilizes a novel proposed two-stage finite impulse response filter with a sampling frequency of 32 kHz, and a very short process time about three samples time. The two approaches are analyzed by presenting theoretical results. Simulated results obtained by simulating a three-phase 230 kV, 50 Hz power transmission line are given that validate the theoretical results, and explicitly verify that the filter based approach has an accuracy of 100% in presence of 10% disturbance while the accuracy of the wavelet transform based approach is maximally 97%, but it has less complication and implementation cost. Another comparative study between this work and other works shows that the two proposed methods have higher accuracy and very shorter process time compared to the other methods, especially in presence of 10% disturbance that actually occurs in power transmission lines.     

A DFT study on the central-ring doped HBC nanographenes

Nanographenes (NGs) are a segment of graphene whose dangling bonds are saturated with hydrogen atoms, introducing different properties and promising applications. Here we investigate the electronic, thermodynamic, optical, and structural properties of four C₃₆X₃Y₃H₁₈ NGs (X = B, and Al; and Y = N, and P) based on the density functional theory calculations. It was mainly found that 1) BN-NG is planar molecule and the others are buckybowl-shaped ones, 2) The bowl-to-bowl inversion Gibbs free energies (ΔG^#) of buckybowl shaped NGs are very huge and the rate constant is very small, hindering the inversion, 3) The relative energetic stability order based on the standard enthalpy of formation (ΔH_f^°) is as BN > AlN > BP > AlP, which the BN, and AlN doped NGs are stable at room temperature but the BP and AlP doped ones are instable, 4) The electrical conductivity order of magnitude is inverse of that of stability, 5) An exciton binding energy is predicted in the range of 0.57–0.75 eV for the NGs which corresponds to Frenkel exciton type, 6) the NGs are not soluble in organic solvent in agreement with the experimental results and is partially soluble in water solvent with Gibbs free energy of solvation (ΔG_solv) in the range of −6.1 to −10.1 kcal/mol.     

Discovery of novel anti-leishmanial agents targeting LdLip3 lipase

Leishmaniasis is a neglected tropical disease, caused by several species of Leishmania. Being an opportunistic lipid-scavenging pathogen, Leishmania relies extensively on lipid metabolism especially for host–pathogen interaction, utilizing host lipids for energy and virulence. The rational approach is to target lipid metabolism of the pathogen focusing lipid-catabolizing lipases. The LdLip3 lipase is considered as drug target as it is constitutively expressed in both promastigote and amastigote forms. Since the LdLip3 structure is not known, we modeled its three-dimensional structure to implement structure-based drug discovery approach. Similarity-based virtual screening was carried out to identify potential inhibitors utilizing NCI diversity set on ZINC database including natural products. Implementing computational and experimental approaches, four anti-leishmanial agents were discovered. The screened molecules ZINC01821375, ZINC04008765, ZINC06117316 and ZINC12653571 had anti-leishmanial activity with IC₅₀ (% viable promastigotes vs. concentration) of 5.2 ± 1.8 μM, 13.1 ± 2.6 μM, 9.4 ± 2.6 μM and 17.3 ± 3.1 μM, respectively. The molecules showed negligible toxicity toward mouse macrophages. Based on the contact footprinting analysis, new molecules were designed with better predicted free energy of binding than discovered anti-leishmanial agents. Further validation for the therapeutic utility of discovered molecules can be carried out by the research community to combat leishmaniasis.     

Tautomeric transformation of temozolomide,their proton affinities and chemical reactivities: A theoretical approach

The gas-phase geometry optimizations of bare, mono- and dihydrated complexes of temozolomide isomers were carried out using density functional calculation at the M06 − 2X/6 − 31 + G(d,p) level of the theory. The structures and protonation energies of protonated species of temozolomide are reported. Chemical indices of all isomers and protonated species are also reported. Energies, thermodynamic quantities, rate constants and equilibrium constants of tautomeric and rotameric transformations of all isomers I1 ↔ TZM ↔ HIa ↔ HIb ↔ I2 ↔ I3 in bare and hydrated systems were obtained.     

Fuzzy logic and statistical-based modelling of the Marshall Stability of asphalt concrete under varying temperatures and exposure times

In this study, the Marshall Stability (MS) of asphalt concrete under varying temperature and exposure times was modelled by using fuzzy logic and statistical method. This is an experimental study conducted using statistics and fuzzy logic methods. In order to investigate the Marshall Stability of asphalt concrete based on exposure time and environment temperature, exposure times of 1.5, 3, 4.5 and 6 h and temperatures of 30, 40 and 50 °C were selected. The MS of the asphalt concrete at 17 °C (in laboratory environment temperature) was used as reference. The results showed that the MS of the asphalt core samples decreased 40.16% at 30 °C after 1.5 h and 62.39% after 6 h. At 40 °C the decrease was 74.31% after 1.5 h, and 78.10% after 6 h. At 50 °C the stability of the asphalt decreased 83.22% after 1.5 h, 88.66% after 6 h. The relationships between experimental results, fuzzy logic model and statistical results exhibited good correlation. The correlation coefficient was R = 0.99 for fuzzy logic model and R² = 0.9 for statistical method. Based on the results of the study, it could be said that both the fuzzy logic method and statistical methods could be used for modelling of the stability of asphalt concrete under varying temperature and exposure time.     

Computational analysis of Amsacrine resistance in human topoisomerase II alpha mutants (R487K and E571K) using homology modeling,docking and all-atom molecular dynamics simulation in explicit solvent

Amsacrine is an effective topoisomerase II enzyme inhibitor in acute lymphatic leukemia. Previous experimental studies have successfully identified two important mutations (R487K and E571K) conferring 100 and 25 fold resistance to Amsacrine respectively. Although the reduction of the cleavage ligand-DNA-protein ternary complex has been well thought as the major cause of drug resistance, the detailed energetic, structural and dynamic mechanisms remain to be elusive. In this study, we constructed human topoisomerase II alpha (hTop2α) homology model docked with Amsacrine based on crystal structure of human Top2β in complex with etoposide. This wild type complex was used to build the ternary complex with R487K and E571K mutants. Three 500 ns molecular dynamics simulations were performed on complex systems of wild type and two mutants. The detailed energetic, structural and dynamic analysis were performed on the simulation data. Our binding data indicated a significant impairment of Amsacrine binding energy in the two mutants compared with the wild type. The order of weakening (R487K > E571K) was in agreement with the order of experimental drug resistance fold (R489K > E571K). Our binding energy decomposition further indicated that weakening of the ligand-protein interaction rather than the ligand-DNA interaction was the major contributor of the binding energy difference between R487K and E571K. In addition, key residues contributing to the binding energy (ΔG) or the decrease of the binding energy (ΔΔG) were identified through the energy decomposition analysis. The change in ligand binding pose, dynamics of protein, DNA and ligand upon the mutations were thoroughly analyzed and discussed. Deciphering the molecular basis of drug resistance is crucial to overcome drug resistance using rational drug design.     

Expansion of the active site of the azoreductase from Shewanella oneidensis MR-1

Azoreductase from Shewanella oneidensis MR-1 (soAzoR) possesses great potential in cleaving azo bond of azo dyes during degradation progress. However, detailed information on interaction of soAzoR with either prosthetic group or substrate remains unavailable, mainly due to the absence of crystallization of soAzoR. In order to unravel these mechanisms, we firstly built the tertiary structure of soAzoR and then computationally predicted the binding mode of FMN, NADH and a model dye, methyl red (MR). Ten residues of soAzoR, which are predicted to participate in ligands binding, were separately substituted for either alanine or phenylalanine to confirm their function. The homologous modeling result reveals soAzoR employs a typical Rossmann fold. In terms of ligand binding modes, the isoalloxazine ring of FMN is stabilized in planar conformation by amino acids in the loop L6 and L9 region. NADH and MR is superposed against the isoalloxazine ring with an angle and the distance from C4 atom of NADH and azo bond of MR to N5 atom of FMN is 4.3 Å and 4.6 Å, respectively. The result of predicted interaction and enzyme kinetic analysis suggests that Asn96, Gly140 and Gly141 are crucial for FMN and MR binding; Tyr119 and Phe161 are more meaningful for NADH binding; Ser16 plays an important role in appropriately binding of both FMN and NADH.