Displaying publications 21 - 40 of 79 in total

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  1. Discovery and Development of Novel Anti-fungal Peptides Against Foodspoiling Fungi
    Muhialdin BJ, Algboory HL, Mohammed NK, Kadum H, Hussin ASM, Saari N, et al.
    Curr Drug Discov Technol, 2020;17(4):553-561.
    PMID: 31309892 DOI: 10.2174/1570163816666190715120038
    BACKGROUND: Despite the extensive research carried out to develop natural antifungal preservatives for food applications, there are very limited antifungal agents available to inhibit the growth of spoilage fungi in processed foods. Scope and Approach: Therefore, this review summarizes the discovery and development of antifungal peptides using lactic acid bacteria fermentation to prevent food spoilage by fungi. The focus of this review will be on the identification of antifungal peptides, potential sources, the possible modes of action and properties of peptides considered to inhibit the growth of spoilage fungi. Key Findings and Conclusions: Antifungal peptides generated by certain lactic acid bacteria strains have a high potential for applications in a broad range of foods. The mechanism of peptides antifungal activity is related to their properties such as low molecular weight, concentration and secondary structure. The antifungal peptides were proposed to be used as bio-preservatives to reduce and/or replace chemical preservatives.
    Matched MeSH terms: Protein Structure, Secondary
  2. Mucoadhesive Low Molecular Chitosan Complexes to Protect rHuKGF from Proteolysis: In-vitro Characterization and FHs 74 Int Cell Proliferation Studies
    Tee YN, Kumar PV, Maki MAA, Elumalai M, Rahman SAKMEH, Cheah SC
    Curr Pharm Biotechnol, 2021;22(7):969-982.
    PMID: 33342408 DOI: 10.2174/1389201021666201218124450
    BACKGROUND: Recombinant Keratinocyte Growth Factor (rHuKGF) is a therapeutic protein used widely in oral mucositis after chemotherapy in various cancers, stimulating lung morphogenesis and gastrointestinal tract cell proliferation. In this research study, chitosan-rHuKGF polymeric complex was implemented to improve the stability of rHuKGF and used as rejuvenation therapy for the treatment of oral mucositis in cancer patients.

    OBJECTIVE: Complexation of rHuKGF with mucoadhesive low molecular weight chitosan to protect rHuKGF from proteolysis and investigate the effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells.

    METHODS: The interaction between chitosan and rHuKGF was studied by molecular docking. Malvern ZetaSizer Nano Zs and Fourier-Transform Infrared spectroscopy (FTIR) tests were carried out to characterize the chitosan-rHuKGF complex. In addition, SDS-PAGE was performed to investigate the interaction between chitosan-rHuKGF complex and pepsin. The effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells was studied by MTT assay.

    RESULTS: Chitosan-rHuKGF complex was formed through the hydrogen bonding proven by the docking studies. A stable chitosan-rHuKGF complex was formed at pH 4.5 and was protected from proteolysis and assessed by SDS PAGE. According to the MTT assay results, chitosan-rHuKGF complex increased the cell proliferation rate of FHs 74 Int cells.

    CONCLUSION: The developed complex improved the stability and the biological function of rHuKGF.

    Matched MeSH terms: Protein Structure, Secondary
  3. Identification of hub glycogenes and their nsSNP analysis from mouse RNA-Seq data
    Firoz A, Malik A, Singh SK, Jha V, Ali A
    Gene, 2015 Dec 15;574(2):235-46.
    PMID: 26260015 DOI: 10.1016/j.gene.2015.08.012
    Glycogenes regulate a large number of biological processes such as cancer and development. In this work, we created an interaction network of 923 glycogenes to detect potential hubs from different mouse tissues using RNA-Seq data. DAVID functional cluster analysis revealed enrichment of immune response, glycoprotein and cholesterol metabolic processes. We also explored nsSNPs that may modify the expression and function of identified hubs using computational methods. We observe that the number of nsSNPs predicted by any two methods to affect protein function is 4, 7 and 2 for FLT1, NID2 and TNFRSF1B. Residues in the native and mutant proteins were analyzed for solvent accessibility and secondary structure change. Analysis of hubs can help in determining their degree of conservation and understanding their functions in biological processes. The nsSNPs proposed in this work may be further targeted through experimental methods for understanding structural and functional relationships of hub mutants.
    Matched MeSH terms: Protein Structure, Secondary
  4. Fulltext Characterization and comparative sequence analysis of the DNA mismatch repair MSH2 and MSH7 genes from tomato
    Tam SM, Samipak S, Britt A, Chetelat RT
    Genetica, 2009 Dec;137(3):341-54.
    PMID: 19690966 DOI: 10.1007/s10709-009-9398-3
    DNA mismatch repair proteins play an essential role in maintaining genomic integrity during replication and genetic recombination. We successfully isolated a full length MSH2 and partial MSH7 cDNAs from tomato, based on sequence similarity between MutS and plant MSH homologues. Semi-quantitative RT-PCR reveals higher levels of mRNA expression of both genes in young leaves and floral buds. Genetic mapping placed MSH2 and MSH7 on chromosomes 6 and 7, respectively, and indicates that these genes exist as single copies in the tomato genome. Analysis of protein sequences and phylogeny of the plant MSH gene family show that these proteins are evolutionarily conserved, and follow the classical model of asymmetric protein evolution. Genetic manipulation of the expression of these MSH genes in tomato will provide a potentially useful tool for modifying genetic recombination and hybrid fertility between wide crosses.
    Matched MeSH terms: Protein Structure, Secondary
  5. Analysis of secondary structure predictions of dengue virus type 2 NS2B/NS3 against crystal structure to evaluate the predictive power of the in silico methods
    Othman R, Wahab HA, Yusof R, Rahman NA
    In Silico Biol. (Gedrukt), 2007;7(2):215-24.
    PMID: 17688447
    Multiple sequence alignment was performed against eight proteases from the Flaviviridae family using ClustalW to illustrate conserved domains. Two sets of prediction approaches were applied and the results compared. Firstly, secondary structure prediction was performed using available structure prediction servers. The second approach made use of the information on the secondary structures extracted from structure prediction servers, threading techniques and DSSP database of some of the templates used in the threading techniques. Consensus on the one-dimensional secondary structure of Den2 protease was obtained from each approach and evaluated against data from the recently crystallised Den2 NS2B/NS3 obtained from the Protein Data Bank (PDB). Results indicated the second approach to show higher accuracy compared to the use of prediction servers only. Thus, it is plausible that this approach is applicable to the initial stage of structural studies of proteins with low amino acid sequence homology against other available proteins in the PDB.
    Matched MeSH terms: Protein Structure, Secondary*
  6. Structure Prediction of a Novel Exo-β-1,3-Glucanase: Insights into the Cold Adaptation of Psychrophilic Yeast Glaciozyma antarctica PI12
    Mohammadi S, Parvizpour S, Razmara J, Abu Bakar FD, Illias RM, Mahadi NM, et al.
    Interdiscip Sci, 2018 Mar;10(1):157-168.
    PMID: 27475956 DOI: 10.1007/s12539-016-0180-9
    We report a detailed structural analysis of the psychrophilic exo-β-1,3-glucanase (GaExg55) from Glaciozyma antarctica PI12. This study elucidates the structural basis of exo-1,3-β-1,3-glucanase from this psychrophilic yeast. The structural prediction of GaExg55 remains a challenge because of its low sequence identity (37 %). A 3D model was constructed for GaExg55. Threading approach was employed to determine a suitable template and generate optimal target-template alignment for establishing the model using MODELLER9v15. The primary sequence analysis of GaExg55 with other mesophilic exo-1,3-β-glucanases indicated that an increased flexibility conferred to the enzyme by a set of amino acids substitutions in the surface and loop regions of GaExg55, thereby facilitating its structure to cold adaptation. A comparison of GaExg55 with other mesophilic exo-β-1,3-glucanases proposed that the catalytic activity and structural flexibility at cold environment were attained through a reduced amount of hydrogen bonds and salt bridges, as well as an increased exposure of the hydrophobic side chains to the solvent. A molecular dynamics simulation was also performed using GROMACS software to evaluate the stability of the GaExg55 structure at varying low temperatures. The simulation result confirmed the above findings for cold adaptation of the psychrophilic GaExg55. Furthermore, the structural analysis of GaExg55 with large catalytic cleft and wide active site pocket confirmed the high activity of GaExg55 to hydrolyze polysaccharide substrates.
    Matched MeSH terms: Protein Structure, Secondary
  7. A bio-mimetic zinc/tau protein as an artificial catalase
    Asadollahi K, Jasemi NS, Riazi GH, Katuli FH, Yazdani F, Sartipnia N, et al.
    Int J Biol Macromol, 2016 Nov;92:1307-1312.
    PMID: 26905468 DOI: 10.1016/j.ijbiomac.2016.02.045
    In this study, the catalase-like activity of monomeric tau protein was reported in the presence of of zinc (Zn(II)) ions at low pH value. Monomeric tau protein contains two SH groups that are a target of disulfide bond formation. However these SH groups are able to interact with Zn(II) ion at pH 7.2 which creates a thiol bond as a mimetic model of chloroperoxidase active site which performs catalase like activity at low pH. Zn(II)/tau protein complex decomposed H2O2 with a high rate (Vm) as well as an efficient turn oven number (kcat) at pH 3. This remarkable catalase like activity is may be attributed to the conformational reorientation of protein at low pH. Circular dichroism (CD) studies did not demonstrate any secondary structural changes of tau protein after addition of Zn(II) ions at pH 7.2. In addition, tau protein shows identical CD bands at pH 7.2 and 3. Moreover, fluorescence quenching of tau by Zn(II) at pH 7.2 was initiated by complex formation rather than by dynamic collision. A significant red shift (6nm) was observed in the emission maximum of the fluorescence spectra when the protein was dissolved at pH 3 compared to pH 7.2. This conformational change can provide information regarding the rearrangements of the protein structure and exposure of Cys-Zn(II) group to the solvent which induces easy access of active site to H2O2 molecules and corresponding enhanced catalytic activity of Zn(II)/tau protein complex. This study introduces tau protein as a bio-inspired high performing scaffold for transition metal encapsulation and introducing an engineered apoprotein-induced biomimetic enzyme.
    Matched MeSH terms: Protein Structure, Secondary
  8. Unravelling protein -organic solvent interaction of organic solvent tolerant elastase from Pseudomonas aeruginosa strain K crystal structure
    Said ZSAM, Arifi FAM, Salleh AB, Rahman RNZRA, Leow ATC, Latip W, et al.
    Int J Biol Macromol, 2019 Apr 15;127:575-584.
    PMID: 30658145 DOI: 10.1016/j.ijbiomac.2019.01.056
    The utilization of organic solvents as reaction media for enzymatic reactions provides numerous industrially attractive advantages. However, an adaptation of enzyme towards organic solvent is unpredictable and not fully understood because of limited information on the organic solvent tolerant enzymes. To understand how the enzyme can adapt to the organic solvent environment, structural and computational approaches were employed. A recombinant elastase from Pseudomonas aeruginosa strain K was an organic solvent tolerant zinc metalloprotease was successfully crystallized and diffracted up to 1.39 Å. Crystal structure of elastase from strain K showed the typical, canonical alpha-beta hydrolase fold consisting of 10-helices (118 residues), 10- β-strands (38 residues) and 142 residues were formed other secondary structure such as loop and coil to whole structure. The elastase from Pseusomonas aeruginosa strain K possess His-140, His-144 and Glu-164 served as a ligand for zinc ion. The conserved catalytic triad was composed of Glu-141, Tyr-155 and His-223. Three-dimensional structure features such as calcium-binding and presence of disulphide-bridge contribute to the stabilizing the elastase structure. Molecular dynamic (MD) simulation of elastase revealed that, amino acid residues located at the surface area and disulphide bridge in Cys-30 to Cys-58 were responsible for enzyme stability in organic solvents.
    Matched MeSH terms: Protein Structure, Secondary
  9. Fulltext A Novel Protein Interaction between Nucleotide Binding Domain of Hsp70 and p53 Motif
    Elengoe A, Naser MA, Hamdan S
    Int J Genomics, 2015;2015:391293.
    PMID: 26098630 DOI: 10.1155/2015/391293
    Currently, protein interaction of Homo sapiens nucleotide binding domain (NBD) of heat shock 70 kDa protein (PDB: 1HJO) with p53 motif remains to be elucidated. The NBD-p53 motif complex enhances the p53 stabilization, thereby increasing the tumor suppression activity in cancer treatment. Therefore, we identified the interaction between NBD and p53 using STRING version 9.1 program. Then, we modeled the three-dimensional structure of p53 motif through homology modeling and determined the binding affinity and stability of NBD-p53 motif complex structure via molecular docking and dynamics (MD) simulation. Human DNA binding domain of p53 motif (SCMGGMNR) retrieved from UniProt (UniProtKB: P04637) was docked with the NBD protein, using the Autodock version 4.2 program. The binding energy and intermolecular energy for the NBD-p53 motif complex were -0.44 Kcal/mol and -9.90 Kcal/mol, respectively. Moreover, RMSD, RMSF, hydrogen bonds, salt bridge, and secondary structure analyses revealed that the NBD protein had a strong bond with p53 motif and the protein-ligand complex was stable. Thus, the current data would be highly encouraging for designing Hsp70 structure based drug in cancer therapy.
    Matched MeSH terms: Protein Structure, Secondary
  10. Fulltext Role of α-helical structure in organic solvent-activated homodimer of elastase strain K
    Rahman RN, Salleh AB, Basri M, Wong CF
    Int J Mol Sci, 2011;12(9):5797-814.
    PMID: 22016627 DOI: 10.3390/ijms12095797
    Recombinant elastase strain K overexpressed from E. coli KRX/pCon2(3) was purified to homogeneity by a combination of hydrophobic interaction chromatography and ion exchange chromatography, with a final yield of 48% and a 25-fold increase in specific activity. The purified protein had exhibited a first ever reported homodimer size of 65 kDa by SDS-PAGE and MALDI-TOF, a size which is totally distinct from that of typically reported 33 kDa monomer from P. aeruginosa. The organic solvent stability experiment had demonstrated a stability pattern which completely opposed the rules laid out in previous reports in which activity stability and enhancement were observed in hydrophilic organic solvents such as DMSO, methanol, ethanol and 1-propanol. The high stability and enhancement of the enzyme in hydrophilic solvents were explained from the view of alteration in secondary structures. Elastinolytic activation and stability were observed in 25 and 50% of methanol, respectively, despite slight reduction in α-helical structure caused upon the addition of the solvent. Further characterization experiments had postulated great stability and enhancement of elastase strain K in broad range of temperatures, pHs, metal ions, surfactants, denaturing agents and substrate specificity, indicating its potential application in detergent formulation.
    Matched MeSH terms: Protein Structure, Secondary*
  11. Fulltext Functional Insights into Silymarin as an Antiviral Agent against Enterovirus A71 (EV-A71)
    Lalani S, Masomian M, Poh CL
    Int J Mol Sci, 2021 Aug 15;22(16).
    PMID: 34445463 DOI: 10.3390/ijms22168757
    Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert virucidal effects, but the binding site on the capsid was unknown. In this study, the ligand interacting site of silymarin was determined in silico and validated in vitro. Moreover, the potential of EV-A71 to develop resistance against silymarin was further evaluated. Molecular docking of silymarin with the capsid of EV-A71 indicated that silymarin binds to viral protein 1 (VP1) of EV-A71, specifically at the GH loop of VP1. The in vitro binding of silymarin with VP1 of EV-A71 was validated using recombinant VP1 through ELISA competitive binding assay. Continuous passaging of EV-A71 in the presence of silymarin resulted in the emergence of a mutant carrying a substitution of isoleucine by threonine (I97T) at position 97 of the BC loop of EV-A71. The mutation was speculated to overcome the inhibitory effects of silymarin. This study provides functional insights into the underlying mechanism of EV-A71 inhibition by silymarin, but warrants further in vivo evaluation before being developed as a potential therapeutic agent.
    Matched MeSH terms: Protein Structure, Secondary
  12. Fulltext The structure and dynamics of BmR1 protein from Brugia malayi: in silico approaches
    Khor BY, Tye GJ, Lim TS, Noordin R, Choong YS
    Int J Mol Sci, 2014 Jun 19;15(6):11082-99.
    PMID: 24950179 DOI: 10.3390/ijms150611082
    Brugia malayi is a filarial nematode, which causes lymphatic filariasis in humans. In 1995, the disease has been identified by the World Health Organization (WHO) as one of the second leading causes of permanent and long-term disability and thus it is targeted for elimination by year 2020. Therefore, accurate filariasis diagnosis is important for management and elimination programs. A recombinant antigen (BmR1) from the Bm17DIII gene product was used for antibody-based filariasis diagnosis in "Brugia Rapid". However, the structure and dynamics of BmR1 protein is yet to be elucidated. Here we study the three dimensional structure and dynamics of BmR1 protein using comparative modeling, threading and ab initio protein structure prediction. The best predicted structure obtained via an ab initio method (Rosetta) was further refined and minimized. A total of 5 ns molecular dynamics simulation were performed to investigate the packing of the protein. Here we also identified three epitopes as potential antibody binding sites from the molecular dynamics average structure. The structure and epitopes obtained from this study can be used to design a binder specific against BmR1, thus aiding future development of antigen-based filariasis diagnostics to complement the current diagnostics.
    Matched MeSH terms: Protein Structure, Secondary
  13. Fulltext Supramolecular Architectures of Nucleic Acid/Peptide Hybrids
    Higashi SL, Rozi N, Hanifah SA, Ikeda M
    Int J Mol Sci, 2020 Dec 12;21(24).
    PMID: 33322664 DOI: 10.3390/ijms21249458
    Supramolecular architectures that are built artificially from biomolecules, such as nucleic acids or peptides, with structural hierarchical orders ranging from the molecular to nano-scales have attracted increased attention in molecular science research fields. The engineering of nanostructures with such biomolecule-based supramolecular architectures could offer an opportunity for the development of biocompatible supramolecular (nano)materials. In this review, we highlighted a variety of supramolecular architectures that were assembled from both nucleic acids and peptides through the non-covalent interactions between them or the covalently conjugated molecular hybrids between them.
    Matched MeSH terms: Protein Structure, Secondary
  14. Crystal structure of truncated haemoglobin from an extremely thermophilic and acidophilic bacterium
    Jamil F, Teh AH, Schadich E, Saito JA, Najimudin N, Alam M
    J. Biochem., 2014 Aug;156(2):97-106.
    PMID: 24733432 DOI: 10.1093/jb/mvu023
    A truncated haemoglobin (tHb) has been identified in an acidophilic and thermophilic methanotroph Methylacidiphilium infernorum. Hell's Gate Globin IV (HGbIV) and its related tHbs differ from all other bacterial tHbs due to their distinctively large sequence and polar distal haem pocket residues. Here we report the crystal structure of HGbIV determined at 1.96 Å resolution. The HGbIV structure has the distinctive 2/2 α-helical structure with extensions at both termini. It has a large distal site cavity in the haem pocket surrounded by four polar residues: His70(B9), His71(B10), Ser97(E11) and Trp137(G8). This cavity can bind bulky ligands such as a phosphate ion. Conformational shifts of His71(B10), Leu90(E4) and Leu93(E7) can also provide more space to accommodate larger ligands than the phosphate ion. The entrance/exit of such bulky ligands might be facilitated by positional flexibility in the CD1 loop, E helix and haem-propionate A. Therefore, the large cavity in HGbIV with polar His70(B9) and His71(B10), in contrast to the distal sites of other bacterial tHbs surrounded by non-polar residues, suggests its distinct physiological functions.
    Matched MeSH terms: Protein Structure, Secondary
  15. NES-REBS: A novel nuclear export signal prediction method using regular expressions and biochemical properties
    Wu T, Wang X, Zhang Z, Gong F, Song T, Chen Z, et al.
    J Bioinform Comput Biol, 2016 06;14(3):1650013.
    PMID: 27225342 DOI: 10.1142/S021972001650013X
    A nuclear export signal (NES) is a protein localization signal, which is involved in binding of cargo proteins to nuclear export receptor, thus contributes to regulate localization of cellular proteins. Consensus sequences of NES have been used to detect NES from protein sequences, but suffer from poor predictive power. Some recent peering works were proposed to use biochemical properties of experimental verified NES to refine NES candidates. Those methods can achieve high prediction rates, but their execution time will become unacceptable for large-scale NES searching if too much properties are involved. In this work, we developed a novel computational approach, named NES-REBS, to search NES from protein sequences, where biochemical properties of experimental verified NES, including secondary structure and surface accessibility, are utilized to refine NES candidates obtained by matching popular consensus sequences. We test our method by searching 262 experimental verified NES from 221 NES-containing protein sequences. It is obtained that NES-REBS runs in 2-3[Formula: see text]mins and performs well by achieving precision rate 47.2% and sensitivity 54.6%.
    Matched MeSH terms: Protein Structure, Secondary
  16. Samira-VP: A simple protein alignment method with rechecking the alphabet vector positions
    Fotoohifiroozabadi S, Mohamad MS, Deris S
    J Bioinform Comput Biol, 2017 Apr;15(2):1750004.
    PMID: 28274174 DOI: 10.1142/S0219720017500044
    Protein structure alignment and comparisons that are based on an alphabetical demonstration of protein structure are more simple to run with faster evaluation processes; thus, their accuracy is not as reliable as three-dimension (3D)-based tools. As a 1D method candidate, TS-AMIR used the alphabetic demonstration of secondary-structure elements (SSE) of proteins and compared the assigned letters to each SSE using the [Formula: see text]-gram method. Although the results were comparable to those obtained via geometrical methods, the SSE length and accuracy of adjacency between SSEs were not considered in the comparison process. Therefore, to obtain further information on accuracy of adjacency between SSE vectors, the new approach of assigning text to vectors was adopted according to the spherical coordinate system in the present study. Moreover, dynamic programming was applied in order to account for the length of SSE vectors. Five common datasets were selected for method evaluation. The first three datasets were small, but difficult to align, and the remaining two datasets were used to compare the capability of the proposed method with that of other methods on a large protein dataset. The results showed that the proposed method, as a text-based alignment approach, obtained results comparable to both 1D and 3D methods. It outperformed 1D methods in terms of accuracy and 3D methods in terms of runtime.
    Matched MeSH terms: Protein Structure, Secondary
  17. Haloadaptation: insights from comparative modeling studies between halotolerant and non-halotolerant dehalogenases
    Edbeib MF, Aksoy HM, Kaya Y, Wahab RA, Huyop F
    J Biomol Struct Dyn, 2020 Aug;38(12):3452-3461.
    PMID: 31422756 DOI: 10.1080/07391102.2019.1657498
    Halophiles are extremophilic microorganisms that grow optimally at high salt concentrations by producing a myriad of equally halotolerant enzymes. Structural haloadaptation of these enzymes adept to thriving under high-salt environments, though are not fully understood. Herein, the study attempts an in silico investigation to identify and comprehend the evolutionary structural adaptation of a halotolerant dehalogenase, DehHX (GenBank accession number: KR297065) of the halotolerant Pseudomonas halophila, over its non-halotolerant counterpart, DehMX1 (GenBank accession number KY129692) produced by Pseudomonas aeruginosa. GC content of the halotolerant DehHX DNA sequence was distinctively higher (58.9%) than the non-halotolerant dehalogenases (55% average GC). Its acidic residues, Asp and Glu were 8.27% and 12.06%, respectively, compared to an average 5.5% Asp and 7% Glu, in the latter; but lower contents of basic and hydrophobic residues in the DehHX. The secondary structure of DehHX interestingly revealed a lower incidence of α-helix forming regions (29%) and a higher percentage of coils (57%), compared to 49% and 29% in the non-halotolerant homologues, respectively. Simulation models showed the DehHX is stable under a highly saline environment (25% w/v) by adopting a highly negative-charged surface with a concomitant weakly interacting hydrophobic core. The study thus, established that a halotolerant dehalogenase undergoes notable evolutionary structural changes related to GC content over its non-halotolerant counterpart, in order to adapt and thrive under highly saline environments.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Protein Structure, Secondary
  18. Molecular dynamics simulations of the adenosine A2a receptor: structural stability, sampling, and convergence
    Ng HW, Laughton CA, Doughty SW
    J Chem Inf Model, 2013 May 24;53(5):1168-78.
    PMID: 23514445 DOI: 10.1021/ci300610w
    Molecular dynamics (MD) simulations of membrane-embedded G-protein coupled receptors (GPCRs) have rapidly gained popularity among the molecular simulation community in recent years, a trend which has an obvious link to the tremendous pharmaceutical importance of this group of receptors and the increasing availability of crystal structures. In view of the widespread use of this technique, it is of fundamental importance to ensure the reliability and robustness of the methodologies so they yield valid results and enable sufficiently accurate predictions to be made. In this work, 200 ns simulations of the A2a adenosine receptor (A2a AR) have been produced and evaluated in the light of these requirements. The conformational dynamics of the target protein, as obtained from replicate simulations in both the presence and absence of an inverse agonist ligand (ZM241385), have been investigated and compared using principal component analysis (PCA). Results show that, on this time scale, convergence of the replicates is not readily evident and dependent on the types of the protein motions considered. Thus rates of inter- as opposed to intrahelical relaxation and sampling can be different. When studied individually, we find that helices III and IV have noticeably greater stability than helices I, II, V, VI, and VII in the apo form. The addition of the inverse agonist ligand greatly improves the stability of all helices.
    Matched MeSH terms: Protein Structure, Secondary
  19. TMDIM: an improved algorithm for the structure prediction of transmembrane domains of bitopic dimers
    Cao H, Ng MCK, Jusoh SA, Tai HK, Siu SWI
    J Comput Aided Mol Des, 2017 Sep;31(9):855-865.
    PMID: 28864946 DOI: 10.1007/s10822-017-0047-0
    [Formula: see text]-Helical transmembrane proteins are the most important drug targets in rational drug development. However, solving the experimental structures of these proteins remains difficult, therefore computational methods to accurately and efficiently predict the structures are in great demand. We present an improved structure prediction method TMDIM based on Park et al. (Proteins 57:577-585, 2004) for predicting bitopic transmembrane protein dimers. Three major algorithmic improvements are introduction of the packing type classification, the multiple-condition decoy filtering, and the cluster-based candidate selection. In a test of predicting nine known bitopic dimers, approximately 78% of our predictions achieved a successful fit (RMSD <2.0 Å) and 78% of the cases are better predicted than the two other methods compared. Our method provides an alternative for modeling TM bitopic dimers of unknown structures for further computational studies. TMDIM is freely available on the web at https://cbbio.cis.umac.mo/TMDIM . Website is implemented in PHP, MySQL and Apache, with all major browsers supported.
    Matched MeSH terms: Protein Structure, Secondary
  20. β Mangostin suppress LPS-induced inflammatory response in RAW 264.7 macrophages in vitro and carrageenan-induced peritonitis in vivo
    Syam S, Bustamam A, Abdullah R, Sukari MA, Hashim NM, Mohan S, et al.
    J Ethnopharmacol, 2014 Apr 28;153(2):435-45.
    PMID: 24607509 DOI: 10.1016/j.jep.2014.02.051
    The fruit hull of Garcinia mangostana Linn. has been used in traditional medicine for treatment of various inflammatory diseases. Hence, this study aims to investigate the in vitro and in vivo anti-inflammatory effect of β mangostin (βM), a major compound present in Garcinia mangostana.
    Matched MeSH terms: Protein Structure, Secondary
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