A study of H2CO•••HF Complex by Advanced Quantum Mechanical Methods

Our research is focused on the ab initio calculations of the equilibrium structures, binding energies, harmonic and anharmonic vibrational frequencies of a hydrogen-bonded complex, which is formed between formaldehyde H2CO and hydrogen fluoride HF, using the Gaussian 09 package of programs with full 6311++G(3df, 3pd) basis sets in the MP2 second-order perturbation theory and CCSD(T) methods. Harmonic and anharmonic vibrational frequencies and intensities of the H2CO···HF complex were calculated by the Gaussian 16 package programs within the same approximation. Geometric changes and frequency shifts at the complex formation were evaluated. The H2CO···HF complex formation energy and the dipole moment were calculated in the CCSD(T)6311++G(3df, 3pd) approximation to be equal, respectively, to 7.78 kcal/mol and 4.2 D. Changes of the geometric, spectral, and energetic parameters of the complex proved the existence of a stable hydrogen bond F–H···O=CH2 between the components.

Blockade of Human α7 Nicotinic Acetylcholine Receptor by α-Conotoxin ImI Dendrimer: Insight from Computational Simulations

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are involved in fast synaptic transmission and mediated physiological activities in the nervous system. α-Conotoxin ImI exhibits subtype-specific blockade towards homomeric α7 and α9 receptors. In this study, we established a method to build a 2×ImI-dendrimer/h (human) α7 nAChR model, and based on this model, we systematically investigated the molecular interactions between the 2×ImI-dendrimer and hα7 nAChR. Our results suggest that the 2×ImI-dendrimer possessed much stronger potency towards hα7 nAChR than the α-ImI monomer and demonstrated that the linker between α-ImI contributed to the potency of the 2×ImI-dendrimer by forming a stable hydrogen-bond network with hα7 nAChR. Overall, this study provides novel insights into the binding mechanism of α-ImI dendrimer to hα7 nAChR, and the methodology reported here opens an avenue for the design of more selective dendrimers with potential usage as drug/gene carriers, macromolecular drugs, and molecular probes.

Identification of Non-Zinc Binding Inhibitors of MMP-2 Through Virtual Screening and Subsequent Rescoring

MMP-2 belongs to a large family of proteases called matrix metalloproteinases (MMPs) that degrades type IV collagen, the main structural component of basement membranes and gelatin. The main pathologic role of MMP-2 overexpression is to contribute to the development of cancer through the progression of metastasis and angiogenesis. A structure-based virtual screening was employed to find new inhibitors with possible selectivity for MMP-2. The inhibitory activities of 3 inhibitors (one was not a suitable drug-like hit) among 19 purchased compounds were approved by enzyme inhibition assay. 5 hits were non-zinc-binding inhibitors of MMP-2. The results demonstrated that a computer-aided drug design could be successfully applied for discovering new MMP-2 inhibitors. We found inhibitors with new scaffolds for the inhibition of MMP-2 with some selectivity features that could be used for future lead optimization processes. According to the docked pose and MD simulation, compound 13 was expected to interact with the S1′ specificity loop of MMP-2 and had 2 π–π interactions and a stable hydrogen bond with the MMP-2 active site. The key feature of compound 13 could be used to guide the design of new non-zinc-binding inhibitors of MMP-2.

Molecular Analysis of Codon 548 in therpoBGene Involved in Mycobacterium tuberculosis Resistance to Rifampin

ABSTRACTMostMycobacterium tuberculosisrifampin-resistant strains have been associated with mutations in an 81-bp rifampin resistance-determining region (RRDR) in the generpoB. However, if this region alone were targeted, rifampin-resistant strains with mutations outside the RRDR would not be detected. In this study, among 51 rifampin-resistant clinical isolates analyzed by sequencing 1,681-bp-long DNA fragments containing the RRDR, 47 isolates contained mutations within the RRDR, three isolates contained mutations both within and outside the RRDR, and only one isolate had a single missense mutation (Arg548His) located outside the RRDR. A drug susceptibility test of recombinantMycobacterium smegmatisandM. tuberculosisisolates carrying mutatedrpoB(Arg548His) showed an increased MIC for rifampin compared to that of the control strains. Modeling of the Arg548His mutant RpoB-DNA complex revealed that the His548 side chain formed a more stable hydrogen bond structure than did Arg548, reducing the flexibility of the rifampin-resistant cluster II region of RpoB, suggesting that the RpoB Arg548His mutant does not effectively interact with rifampin and results in bacterial resistance to the drug. This is the first report on the relationship between the mutation in codon 548 of RpoB and rifampin resistance in tuberculosis. The novel mutational profile of therpoBgene described here will contribute to the comprehensive understanding of rifampin resistance patterns and to the development of a useful tool for simple and rapid drug susceptibility tests.

The Study of Glycerol Plasticized Thermoplastic Sago Starch

Thermoplastic sago starch (TPSS) was produced by plasticizing with glycerol through melt blending before being compression moulded. The investigated TPSS was prepared at glycerol/starch weight fraction of 40/60, 35/65 and 30/70. The functional groups composition, tensile strength, density, moisture content and water absorption were evaluated and compared at different glycerol/starch ratio. The compatibility of the glycerol as the plasticizer in the TPSS was proven by Fourier transform infrared spectroscopy (FTIR) where glycerol could form stable hydrogen bond with sago starch. This preliminary study demonstrated that the stress at maximum load was only applicable for lower glycerol/starch ratio of 30/70. The density of TPSS was inversely proportional to the increment of glycerol/starch ratio whereas moisture content and water absorption had opposite relationship.