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91.
Gholamhossein Sodeifian Fariba Razmimanesh 《Journal of biomolecular structure & dynamics》2019,37(7):1666-1684
In this research, for the first time, molecular dynamics (MD) method was used to simulate aspirin and ibuprofen at various concentrations and in neutral and charged states. Effects of the concentration (dosage), charge state, and existence of an integral protein in the membrane on the diffusion rate of drug molecules into lipid bilayer membrane were investigated on 11 systems, for which the parameters indicating diffusion rate and those affecting the rate were evaluated. Considering the diffusion rate, a suitable score was assigned to each system, based on which, analysis of variance (ANOVA) was performed. By calculating the effect size of the indicative parameters and total scores, an optimum system with the highest diffusion rate was determined. Consequently, diffusion rate controlling parameters were obtained: the drug–water hydrogen bond in protein-free systems and protein–drug hydrogen bond in the systems containing protein. 相似文献
92.
Wenbo Yu Sunhwan Jo Sirish Kaushik Lakkaraju David J. Weber Alexander D. MacKerell Jr 《Proteins》2019,87(4):289-301
Protein docking methods are powerful computational tools to study protein-protein interactions (PPI). While a significant number of docking algorithms have been developed, they are usually based on rigid protein models or with limited considerations of protein flexibility and the desolvation effect is rarely considered in docking energy functions, which may lower the accuracy of the predictions. To address these issues, we introduce a PPI energy function based on the site-identification by ligand competitive saturation (SILCS) framework and utilize the fast Fourier transform (FFT) correlation approach. The free energy content of the SILCS FragMaps represent an alternative to traditional energy grids and they can be efficiently utilized to guide FFT-based protein docking. Application of the approach to eight diverse test cases, including seven from Protein Docking Benchmark 5.0, showed the PPI prediction using SILCS approach (SILCS-PPI) to be competitive with several commonly used protein docking methods indicating that the method has the ability to both qualitatively and quantitatively inform the prediction of PPI. Results show the utility of the SILCS-PPI docking approach for determination of probability distributions of PPI interactions over the surface of both partner proteins, allowing for identification of alternate binding poses. Such binding poses are confirmed by experimental crystal contacts in our test cases. While more computationally demanding than available PPI docking technologies, we anticipate that the SILCS-PPI docking approach will offer an alternative methodology for improved evaluation of PPIs that could be used in a variety of fields from systems biology to excipient design for biologics-based drugs. 相似文献
93.
NSAIDs are potent chemopreventive agents for colon cancer. Although their mechanism of action is unknown, it probably relates to their modulation of colon epithelial cell kinetics, i.e. apoptosis and/or cell proliferation. NSAIDs are pleiotropic in their biochemical activities; their best known effect is inhibition of prostaglandin H synthase (PHS), the enzyme catalyzing the biosynthesis of prostaglandins. Current data appear to lead to two conflicting conclusions. One body of data indicates that PHS is important in induction of apoptosis and colon carcinogenesis and that its inhibition by NSAIDs is required for induction of apoptosis and their overall chemopreventive effect. Another set of data indicates that NSAIDs may induce apoptosis and prevent colon cancer without inhibiting the activity of PHS. Both sides of this argument are presented and discussed. This apparent contradiction may be resolved if one accepts that both mechanisms are correct but that they act on different steps of this multistep process. 相似文献
94.
L-Histidine is a beneficial adjuvant for antiepileptic drugs against maximal electroshock-induced seizures in mice 总被引:2,自引:0,他引:2
Summary. Endogenous histamine has been reported to be involved in regulation of seizure susceptibility. Enhancement of histamine neurotransmission engendered by L-histidine treatment produces anticonvulsant effects in experimental animals. The present study investigated the influence of L-histidine on the protective effects of carbamazepine and phenytoin against maximal electroshock-induced seizures in mice.L-Histidine, administered at the doses that did not influence the threshold for electroconvulsions (250–500mg/kg), enhanced by nearly 30% the protective effects of carbamazepine against maximal electroshock-induced seizures. D-Histidine (1000mg/kg), an inactive isomer of histidine, was without any effect in this regard. L-Histidine (500mg/kg) also augmented the protective effects of phenytoin. Importantly, the enhancement of the anticonvulsant effects of these antiepileptic drugs produced by L-histidine co-administration was not associated with augmentation of their unwanted effects on memory and motor performance. A pharmacokinetic interaction was also excluded since the free plasma levels of these antiepileptics remained unchanged in the presence of L-histidine. It may be suggested that L-histidine could serve as a beneficial adjuvant for selected antiepileptic drugs.Present address: Integrative Neuroscience Section, Behavioral Neuroscience Branch, NIDA/NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, U.S.A. 相似文献
95.
Neuroprotective Mechanisms of Antiparkinsonian Dopamine D2-Receptor Subfamily Agonists 总被引:2,自引:0,他引:2
Numerous studies have shown that endogenous and/or environmental neurotoxins and oxidative stress may participate in the pathogenesis of Parkinson's disease (PD), but the detailed mechanisms are still unclear. While dopamine (DA) replacement therapy with L-DOPA (levodopa) improves PD symptoms, it does not inhibit the degeneration of DA neurons in the substantia nigra. Recently, bromocriptine, pramipexole and several other agonists of the dopamine D2-receptor subfamily (including D2, D3 and D4-subtypes) have been shown to have neuroprotective effects in parkinsonian models in vitro and in vivo. Their neuroprotective effects may be mediated directly and/or indirectly by antioxidant effects, mitochondrial stabilization or induction of the antiapoptotic Bcl-2 family. 相似文献
96.
The cortical serotonin2A receptor and the pathology of schizophrenia: a likely accomplice 总被引:2,自引:0,他引:2
Dean B 《Journal of neurochemistry》2003,85(1):1-13
A large body of evidence shows that there is a change in the density of cortical serotonin2A receptors (5HT2AR) in post-mortem CNS from subjects with schizophrenia. Furthermore, some antipsychotic drugs have also been shown to cause a decrease in the density of 5HT2AR in the rat CNS. Thus, it appeared possible that changes in this receptor in human post-mortem CNS simply reflected an antipsychotic drug effect. However, a great deal of research on the 5HT2AR and schizophrenia now suggests that the changes in this receptor are complex and may be involved in both the pathology of the disorder and the effects of some antipsychotic drugs. Moreover, recent advances in basic research on the role of the 5HT2AR in the CNS add further support to the hypothesis that the receptor could be involved in the pathology of the illness. In particular, an argument will be developed that the changes in the 5HT2AR in schizophrenia are reflective of a real or perceived change in serotonergic tone and that this forms an important part of the pathology of the illness. 相似文献
97.
Antipsychotic drugs have been reported to increase the expression of subunits of the NMDA receptor at the level of mRNA but it is not clear whether such effects are apparent at the level of the radioligand binding or receptor protein. Therefore, we examined the effect of treatment of, and withdrawal from, haloperidol, chlorpromazine, olanzapine or clozapine on the binding of [3H]N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP ) to the open ion channel of the NMDA receptor in rat caudate-putamen, hippocampus and frontal cortex. [3H]TCP binding was not significantly different in the caudate-putamen, hippocampus and cortex after three months of treatment with any antipsychotic drug. There were significant decreases in [3H]TCP binding in rat caudate-putamen and cortex, but not hippocampus, one month after ceasing treatment. Decreases in the caudate-putamen were detected in rats previously treated with chlorpromazine (0.1 mg/kg/day) and clozapine (0.1 and 1.0 mg/kg/day). In the cortex, decreases in [3H]TCP binding were also detected in rats previously treated with olanzapine (0.1 mg/kg/day) for three months. These data suggest that changes in the NMDA receptor associated ion channels occur following antipsychotic drug withdrawal. 相似文献
98.
99.
Canarelli S Fisch I Freitag R 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,775(1):27-35
A robust tool is proposed for the rapid at-line verification of the identity and integrity of (recombinant) proteins, namely the hyphenation of multidimensional chromatography and mass spectrometry (MS). A recombinant human antibody produced in Chinese hamster ovary cells is taken as pertinent example. The recombinant human antibody is first captured from the production environment by affinity chromatography (rProtein A, isolation/concentration of the target molecule) and automatically transferred to an enzyme reactor (immobilized trypsin column) for digestion, thereby yielding different peptides corresponding to the protein sequence. The peptides are then separated on a reversed-phase column before being analyzed and identified by MS. This step does not require a fine resolution since the mass spectrometer can identify a variety of substances at the same time. The results are then analyzed in silico with suitable bio-informatic tools. When the gene sequence of the protein product is known, proteolytic cleavages can be predicted and the exact mass and hence the amino acid sequence of each peptide can thereby be deduced. Fitting experimental data and reference peptide sequences then provides important information about the integrity of the protein and more particularly about its sequence. In our case, the integrity of 45% of the light and 75% of the heavy chain sequences of the antibody could be verified within minutes. 相似文献
100.
In the present work, we measured survival and the platinum on the genome after treatment of repair-proficient or repair-deficient Escherichia coli strains with trans-[PtCl2(E-iminoether)2] and compared these results with the effects of “classical” cisplatin. We found that toxicity of antitumor trans-[PtCl2(E-iminoether)2] in repair-deficient trains was much less than that of cisplatin. This markedly reduced toxicity was not a consequence of the reduced uptake or low levels of DNA binding in the bacteria cells but rather appeared to reflect DNA binding mode of this trans-platinum drug different from that of cisplatin. 相似文献