Protein Modeling

To determine the frequency of hepatoma in patients with cirrhosis attending tertiary care hospital Karachi. Study Period: Six months July to December 2017. Study Design: Descriptive cross sectional study. Setting: Department of Gastroenterology, Liaquat National postgraduate Medical centre Karachi. Patients and Methods: The clinical history was taken from patients and ultrasound of liver was done to and mass if any and its size was noted. Noninvasive criteria for diagnosing hepatoma were utilized and all information was noted and entered in the proforma and analyzed in statistical software. Results: A total of 213 cases, 15.02% individual hepatitis B and 21.13% subject hepatitis C. Frequency of hepatoma in cirrhotic population detected as 10.33% (22/213). Rate of hepatoma was not significant among different age groups (p=0.202). Rate of hepatoma was also not significant between male and female (p=0.59). Conclusion: Persistent chronic viral hepatitis B and C infection with cirrhosis responsible for acquiring hepatoma.

Laboratorul de biochimie, Catedra de biochimie şi biochimie clinică, IP USMF “Nicolae Testemițanu”, Laboratorul de imunologie, Institutul de Ftiziopulmonologie „Chiril Draganiuc”În lucrare sunt prezentate rezultatele cercetării infl uenţei polizaharidelor sulfatate extrase din biomasa cianobacteriei Spirulina platensis (PSS) asupra indicilor stresului oxidativ și activităţii unor enzime antioxidante în măduva osoasă în condiţii fi ziologice şi la modelarea hepatitei toxice. Material și metode. Cercetările au fost efectuate in vivo pe 32 şobolani adulţi. Hepatopatia experimentală a fost indusă cu tetraclorură de carbon (CCl4 ). Rezultate. S-a constatat că la animalele intacte PSS reduce intensitatea proceselor de oxidare cu radicali liberi – scade nivelul DAM, AOPP, S-nitrozotioli și AGEs în măduva osoasă, fapt ce denotă efectul antioxidant al acestui preparat. PSS, deasemenea, reușește să reducă intensitatea efectelor toxice ale CCl4 asupra celulelor măduvei osoase prin tendința de ...

The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3 ′ end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Compuşii biologici activi (CBA) cercetaţi exercită efect stimulator pronunţat asupra proceselor de hidroliză enzimatică a matricei extracelulare hepatice în ciroza hepatică (CH), contribuind la catabolizarea mai efi cientă a ţesutului fi bros, fenomen probat de reducerea nivelului de acizi uronici. Stimularea proceselor litice în fi catul cirozat, realizată de CBA luaţi în studiu, este specifi că şi dependentă de gradul de angajare a enzimelor lizozomale implicate în procesele de degradare a ţesutului conjunctiv

A set of 16 previously synthesized aryl-aminopyridine and aryl-aminoquinoline derivatives have been evaluated for cytotoxic activity against three cancer cell lines (human cervical cancer-HeLa; human chronic myeloid leukemia-K562; human melanoma-Fem-x) and two types of normal peripheral blood mononuclear cells, with and without phytohemaglutinin (PBMC À PHA; PBMC + PHA). Twelve of the studied compounds showed moderate cytotoxicity, with selectivity against K562 but not the remaining two cancer cell lines. Four compounds were not active in cytotoxicity assays, presumably due to high predicted lipophilicity and low solubility. To rationalize the observed cytotoxic effects, structure-based virtual screening was carried out against a pool of potential targets constructed using the inverse docking program Tarfisdock and bibliographical references. The putative targets were identified on the basis of the best correlation between docking scores and in vitro cytotoxicity. It is proposed that the mechanism of action of the studied aminopyridines involves the disruption of signaling pathways and cancer cell cycle through the inhibition of cyclin-dependent kinases and several tyrosine kinases, namely Bcr-Abl kinase and KIT receptor kinase. The obtained results can guide further structural modifications of the studied compounds aimed at developing selective agents targeting proteins involved in cancer cell survival and proliferation.

The emergence of resistance to the first-line antimalarial drugs poses
a significant threat to recent progress in the fight against malaria. It is
imperative to discover novel therapeutic drugs for Malaria. Utilizing rational
methods facilitated by bioinformatics tools presents the most efficient and
cost-effective approach to achieve this imperative. The objective of this
study was: first, to model an active structure of Plasmepsin X (PlmX) a
potent multistage drug target from Plasmodium falciparum, and second,
to identify potential inhibitors from African databases of Natural Products.
The model was constructed utilizing a multiple templates approach
implemented in Modeller. The best model obtained underwent validation
using standard tools. Subsequently, a high throughput virtual screening
was conducted using Autodock Vina, employing African databases of
Natural Products. The results demonstrated the successful construction of
an accurate and validated model of PlmX.

Berbagai senyawa alam telah dilaporkan dapat digunakan sebagai antikanker namun demikian mekanisme aksinya belum dapat ditentukan secara jelas. Salah satu senyawa dalam tanaman adalah acetogenin yang dapat menginduksi apoptosis dalam studi in vitro. Dua acetogenin terbaru yang ditemukan dalam Annona muricata adalah annomuricin E dan muricapentocin. Molecular docking merupakan salah satu model in silico untuk skrining senyawa berdasarkan mekanismenya terhadap protein. Oleh karena itu, kedua senyawa ini didocking menggunakan PLANTS 1.1 untuk melihat afinitasnya dengan protein proliferasi, yaitu Protein Kinase C. Perhitungan RMSD terhadap letak ikatan prediksi terbaik memberikan nilai sebesar 1,3906 Å. Hasil molecular docking dari senyawa referens (07u), annomuricin E dan muricapentocin menunjukkan skor kestabilan interaksi masing-masing sebesar-71,161;-127,739; dan-116,868. Hal ini menunjukkan annomuricin E memiliki afinitas terbaik terhadap Protein Kinase C dan dapat menghambat proliferasi lebih baik dibandingkan senyawa referens dan muricapentocin.

Geobacter sulfurreducens pili are -implicated in facilitating electron transfer to electrode surfaces. Comparisons are made between the conductivity of pili and that of doped organic semi-conductors, invoking mechanisms such as "electron hopping" or "metallic conduction". Ana-lysis of inter-aromatic distances in these pili models shows that charge-carrier transport involving only the π-conjugated system of GS pili is negligible.

Victor Ghicavîi, membru corespondent al AŞM, dr. hab. şt. med., prof. univ., Catedra de farmacologie şi farmacologie clinică) Introducere. Cercetarea noilor derivaţi izotioureici în ultimii ani a atins proporţii semnificative. În fond sunt cunoscuţi ca substanţe vasoconstrictoare efective, posibil de utilizat în hipotensiunea arterială. Ultimele studii ale acestor derivaţi au evidenţiat o substanţă cu acţiune hipotensivă clorură-Sbenzilizotiouroniu (benzituron). Scopul lucrării. Elucidarea experimentală a influenţei benzituronului asupra consumului de oxigen la animalele de laborator. Material şi metode. Consumul de oxigen s-a determinat timp de 3 min cu ajutorul instalaţiei S.V. Miropolski la intervalele de timp: 1-3 min; 5-8 min; 15-18 min; 30-33 min; 60-63 min; 120-123 min. În experienţă au fost incluse 2 loturi de şobolani de linie Wistar, câte 10 în fiecare, cu masa 208-320g. Şobolanilor din lotul martor le-am administrat intraperitoneal 2 ml de soluţie fiziologică, celor din lotul test, benzituron în doză de 2 mg/kg masă corporală. Prelucrarea statistică după criteriul t-Student. Rezultate. În intervalele de timp 1-3 min; 5-8 min; 15-18 min; 30-33 min nu au fost determinate diferenţe semnificative statistice a valorii medii a consumului de oxigen dintre lotul test şi lotul martor. În schimb s-a constatat o diferenţă a valorilor medii dintre lotul martor: 19.61±0,95 la 60-63 min; 17.54±0,43 la 120-123 min şi lotul test: 14,36±1,33 la 60-63min; 11,22±1,55 la 120-123 min, unde p=0,004 pentru 60-63 min; iar pentru 120-123 min, p=0,001. Concluzii. În rezultatul experienţelor s-a observat o micşorare a consumului de oxigen la administrarea benzituronului comparativ cu lotul martor. Micşorarea a fost semnificativă începînd cu minutul 60. Cuvinte cheie: benzituron, consum de oxigen.

Streptomyces canus are Gram-positive bacteria belonging to family Streptomycetaceae. It has major medicinal utilities and can be used for producing anti-bacterial, anti-parasitic, anti-fungal drugs and immunosuppressants. In recent years, Streptomyces has come up as a use for retrieval of heterogeneous expression of protein, in biotechnology. This study involved computational approach for the determination of structural properties of the protease. The physcio-chemical properties prediction was done by using Protparam. The secondary structure prediction has been carried with GOR4 prediction tool, predicting the alpha-beta helices of the protease sequences. 3-D structure of the protease has been predicted using homology modeling methods. The structural studies will provide a better insight to the functional analysis.

Structural characterization of protein-protein interactions is essential for our ability to understand life processes. However, only a fraction of known proteins have experimentally determined structures. Such structures provide templates for modeling of a large part of the proteome, where individual proteins can be docked by template-free or template-based techniques. Still, the sensitivity of the docking methods to the inherent inaccuracies of protein models, as opposed to the experimentally determined high-resolution structures, remains largely untested, primarily due to the absence of appropriate benchmark set(s). Structures in such a set should have pre-defined inaccuracy levels and, at the same time, resemble actual protein models in terms of structural motifs/packing. The set should also be large enough to ensure statistical reliability of the benchmarking results. We present a major update of the previously developed benchmark set of protein models. For each interactor, six models were generated with the model-to-native C α RMSD in the 1 to 6 Å range. The models in the set were generated by a new approach, which corresponds to the actual modeling of new protein structures in the "real case scenario," as opposed to the previous set, where a significant number of structures were model-like only. In addition, the larger number of complexes (165 vs. 63 in the previous set) increases the statistical reliability of the benchmarking. We estimated the highest accuracy of the predicted complexes (according to CAPRI criteria), which can be attained using the benchmark structures. The set is available at http://dockground.bioinformatics.ku.edu.

Structural characterization of protein-protein interactions is important for understanding life processes. Because of the inherent limitations of experimental techniques, such characterization requires computational approaches. Along with the traditional protein-protein docking (free search for a match between two proteins), comparative (template-based) modeling of protein-protein complexes has been gaining popularity. Its development puts an emphasis on full and partial structural similarity between the target protein monomers and the protein-protein complexes previously determined by experimental techniques (templates). The template-based docking relies on the quality and diversity of the template set. We present a carefully curated, non-redundant library of templates containing 4,950 full structures of binary complexes and 5,936 protein-protein interfaces extracted from the full structures at 12Å distance cutoff. Redundancy in the libraries was removed by clustering the PDB structures based on structural similarity. The value of the clustering threshold was determined from the analysis of the clusters and the docking performance on a benchmark set. High structural quality of the interfaces in the template and validation sets was achieved by automated procedures and manual curation. The library is included in the Dockground resource for molecular recognition studies at http:// dockground.bioinformatics.ku.edu.

Characterization of life processes at the molecular level requires structural details of proteinprotein interactions (PPIs). The number of experimentally determined protein structures accounts only for a fraction of known proteins. This gap has to be bridged by modeling, typically using experimentally determined structures as templates to model related proteins. The fraction of experimentally determined PPI structures is even smaller than that for the individual proteins, due to a larger number of interactions than the number of individual proteins, and a greater difficulty of crystallizing protein-protein complexes. The approaches to structural modeling of PPI (docking) often have to rely on modeled structures of the interactors, especially in the case of large PPI networks. Structures of modeled proteins are typically less accurate than the ones determined by X-ray crystallography or nuclear magnetic resonance. Thus the utility of approaches to dock these structures should be assessed by thorough benchmarking, specifically designed for protein models. To be credible, such benchmarking has to be based on carefully curated sets of structures with levels of distortion typical for modeled proteins. This article presents such a suite of models built for the benchmark set of the X-ray structures from the DOCKGROUND resource (http:// dockground.bioinformatics.ku.edu) by a combination of homology modeling and Nudged Elastic Band method. For each monomer, six models were generated with predefined C α root mean square deviation from the native structure (1, 2,. . ., 6 Å). The sets and the accompanying data provide a comprehensive resource for the development of docking methodology for modeled proteins.

Breast cancer is one of the leading cancer types in women across the world. Computer aided drug designing have been widely applied for drug development and discovery of potential drug molecule of many over expressed proteins induced in breast cancer. In the present study HIF-1a is targeted as receptor and peptides targeted as ligands through protein-protein interaction. A total of 352 peptides were docked with the predicted binding sites of HIF-1a and found that 9 peptides exhibited encouraging binding and docking energy. The maximum docking interactions score of À38.15 kJ/mol was observed between a peptide FALALKA and HIF-1a. By analyzing docking study results, amino acid Aspartic acid (Asp 187) play a crucial role forming H-bond and hydrophobic interactions with all the 9 peptides. Taken together, the results of present findings throws light on the design of novel HIF-1a antagonist peptides and aspartic acid could considered during its design for implying its action as a best antagonist against the HIF-1a receptor.

Producerea de oxidanți este inevitabilă în organismele aerobe inclusiv în corpul uman care deține un sistem antioxidant complex de apărare. Există un echilibru între oxidanți și antioxidanți. Dacă acest echilibru este modificat în favoarea oxidanților atunci apare stresul oxidativ.(20) Scopul studiului: Scopul acestui studiu a fost de a evalua markerii stresului oxidativ în serul şi în saliva femeilor gravide cu carii dentare şi gingivită şi de a investiga utilizarea de metode simple de laborator de determinare a unor antioxidanți precum ceruloplasmina, acidul uric în evaluarea clinică şi tratamentul afecţiunilor dentare. Material și metodă: Cercetările noastre au fost efectuate pe 27 de femei gravide sănătoase cu vârsta cuprinsă între 18 şi 39 ani, în a cincea şi a noua lună de sarcină, selectate dintre pacientele Spitalului de Obstetrică-Ginecologie, Oradea. Rezultatele au fost comparate cu un grup de control asemănător cu grupul de studiu privind vârsta, IMC (index de masă corporal), tensiunea arterială. Pentru demonstrarea stresului oxidativ am dozat concentraţia malondialdehidei utilizând metoda cu acid tiobarbituric (TBA) şi a ceruloplasminei cu metoda Ravin. Analize suplimentare precum acidul uric, fierul şi proteina C reactivă s-au făcut pe analizorul HITACHI 912 Roche Diagnostics și folosind reactiv Greiner Diagnostic, Germania. Rezultate și discuții: MDA salivară a fost mai mare în ambele grupuri studiate, comparativ cu grupul martor. Concentraţia salivară a ceruloplasminei este mai mică la gravidele cu carii dentare sau cu gingivită, în comparaţie cu grupul de control. Nu am obţinut diferenţe semnificative ale concentraţiei acidului uric atât în ser, cât şi în salivă la gravide comparativ cu grupul de control. Valorile proteinei C reactive în salivă s-au aflat sub limita de detecție a metodei (<0.8mg/dl). Concluzii: Indicatorii agresiunii oxidative dozaţi pot oferi un instrument de monitorizare a stării de sănătate orală a gravidelor.

Objective: A wide range of toxic effects against other species are affected through potential protein molecules called neurotoxins. Among various kinds of toxins, neurotoxins play a critical role in life of other organisms (especially humans). So it is relatively important to know more about neurotoxins and their action on biological systems. All around the world several research works are progressing in the area of neurotoxins. Methods: Here we present NEUROTOX, a database which contains more than 1400 toxin entries originating from more than ~248 different species. The data was enriched with the related data derived from various other protein sequence as well as structural databases and several literature resources. Each entry of toxin contains 18 fields providing detailed information on neurotoxins and their source, fasta formatted protein sequences, molecular weight, toxicity information along with their literature references. Results: In addition, 1086 computationally resolved 3D structures of toxin proteins with validation results were made available for download. Conclusion: The easy to use and freely accessible NEUROTOX database is available online at http: //www. neuro-tox. org and it provides the large range data on toxins.

Fasciclin 111 is an integral membrane protein expressed on a subset of axons in the developing Drosophila nervous system. It consists of an intracellular domain, a transmembrane region, and an extracellular region composed of three domains, each predicted to form an immunoglobulin-like fold. The most N-terminal of these domains is expected to be important in mediating cell-cell recognition events during nervous system development. To learn more about the structure/function relationships in this cellular recognition molecule, a model structure of this domain was built. A sequence-to-structure alignment algorithm was used to align the protein sequence of the fasciclin I11 first domain to the immunoglobulin McPC603 structure. Based on this alignment, a model of the domain was built using standard homology modeling techniques. Side-chain conformations were automatically modeled using a rotamer search algorithm and the model was minimized to relax atomic overlaps. The resulting model is compact and has chemical characteristics consistent with related globular protein structures. This model is a de novo test of the sequence-to-structure alignment algorithm and is currently being used as the basis for mutagenesis experiments to discern the parts of the fasciclin I11 protein that are necessary for homophilic molecular recognition in the developing Drosophila nervous system.

ABSTRACT: Colorectal cancer is cancer that grows in the colon (large intestine) or in the lower colon that is connected to the rectum. Anticolorectal Cancer activity is found in the soursop plant (Annona muricata) which contains annomuricin compounds. The EGFR receptor is a receptor that plays an important role in anticancer activity. The purpose of this study was to prove based on in silico study whether the annomuricin compounds could be used as a anticancer candidate. The identification of the physicochemical properties of annomuricin compounds was carried out using ChemBioDraw 2D software. The annomuricin compound was optimized using Gauss View software version 5.0.8 and Gaussian version 09. Then proceed to the docking simulation to EGFR receptor which has been separated from its natural ligand validation of molecular docking system was carried out using MGL Tools 1.5.6 software which has been equipped with Autodock Tools version 4.2. The result showed that annomuricin D compoun...

The remarkable rise of the current COVID-19 pandemic to every part of the globe has raised key concerns for the current public healthcare system. The spike (S) protein of SARS-CoV-2 shows an important part in the cell membrane fusion and receptor recognition. It is a key target for vaccine production. Several researchers studied the nature of this protein under various environmental conditions. In this work, we applied molecular modeling and extensive molecular dynamics simulation approaches at 0°C (273.15 K), 20°C (293.15 K), 40°C (313.15 K), and 60°C (333.15 K) to study the detailed conformational alterations in the SARS-CoV-2 S protein. Our aim is to understand the influence of temperatures on the structure, function, and dynamics of the S protein of SARS-CoV-2. The structural deviations, and atomic and residual fluctuations were least at low (0°C) and high (60°C) temperature. Even the internal residues of the SARS-CoV-2 S protein are not accessible to solvent at high temperature...

Development of new drugs is a time-taking and expensive process. Comprehensive efforts are being made globally toward the search of therapeutics against SARS-CoV-2. Several drugs such as remdesivir, favipiravir, ritonavir, and lopinavir have been included in the treatment regimen and shown effective results in several cases. Among the existing broad-spectrum antiviral drugs, remdesivir is found to be more effective against SARS-CoV-2. Remdesivir has broad-spectrum antiviral action against many single-stranded RNA viruses including pathogenic SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). In this study, we proposed that remdesivir strongly binds to membrane protein (Mprotein), RNA-dependent RNA polymerase (RDRP), and main protease (Mprotease) of SARS-CoV-2. It might show antiviral activity by inhibiting more than one target. It has been found that remdesivir binds to Mprotease, Mprotein, and RDRP with −7.8, −7.4, and −7.1 kcal/mol, respectively. The structure d...

Sphingosine kinase 1 (SphK1) is a promising therapeutic target against several diseases including mammary cancer. The aim of present work is to identify a potent lead compound against breast cancer using ligand-based virtual screening, molecular docking, MD simulations, and the MMPBSA calculations. The LBVS in molecular and virtual libraries yielded 20,800 hits, which were reduced to 621 by several parameters of drug-likeness, lead-likeness, and PAINS. Furthermore, 55 compounds were selected by ADMET descriptors carried forward for molecular interaction studies with SphK1. The binding energy (DG) of three screened compounds namely ZINC06823429 (-11.36 kcal/mol), ZINC95421501 (-11.29 kcal/mol), and ZINC95421070 (-11.26 kcal/mol) exhibited stronger than standard drug PF-543 (-9.9 kcal/mol). Finally, it was observed that the ZINC06823429 binds tightly to catalytic site of SphK1 and remain stable during MD simulations. This study provides a significant understanding of SphK1 inhibitors that can be used in the development of potential therapeutics against breast cancer.

Based on a protein-protein docking approach we have developed a procedure to verify or falsify protein-protein interactions that were proposed by other methods such as yeast-2-hybrid assays. Our method currently utilizes intermolecular energies but can be expanded to incorporate additional terms such as amino acid based pair-potentials. We show some early results that demonstrate the general applicability of our approach.

We present the results for CAPRI Round 46, the third joint CASP‐CAPRI protein assembly prediction challenge. The Round comprised a total of 20 targets including 14 homo‐oligomers and 6 heterocomplexes. Eight of the homo‐oligomer targets and one heterodimer comprised proteins that could be readily modeled using templates from the Protein Data Bank, often available for the full assembly. The remaining 11 targets comprised 5 homodimers, 3 heterodimers, and two higher‐order assemblies. These were more difficult to model, as their prediction mainly involved “ab‐initio” docking of subunit models derived from distantly related templates. A total of ~30 CAPRI groups, including 9 automatic servers, submitted on average ~2000 models per target. About 17 groups participated in the CAPRI scoring rounds, offered for most targets, submitting ~170 models per target. The prediction performance, measured by the fraction of models of acceptable quality or higher submitted across all predictors groups...

The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3 ′ end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Penelitian ini dilakukan untuk menentukan senyawa turunan kalkon yang berpotensi sebagai antikanker payudara berdasarkan Molecular Docking. Protein yang digunakan yaitu 17β-hidroksisteroid dehydrogenase. Adapun ligan yang digunakan adalah 20 senyawa turunan kalkon yang dibandingkan dengan senyawa obat pembanding. Posisi pusat grid pada sisi aktif protein kanker payudara yang telah dilakukan pada penelitian sebelumnya yaitu pada leusin 149.X CB, serin 142.X OG, dan asparagine 152.X OD1. Software yang digunakan yaitu hyperchem, Gaussian03, Molden, Autodock Tools, Autodock4, dan chimera 1.5.3. Penelitian ini dilakukan dengan empat langkah yaitu pencarian kompleks protein-ligan 17β-hidroksisteroid dehydrogenase dengan kode PDB 3HB4, optimasi struktur ligan dengan metode perhitungan AM1, molecular docking, dan pemilihan senyawa turunan kalkon sebagai antikanker payudara. Hasil docking turunan kalkon memiliki akivitas daya hambat terhapat protein 17β-hidroksisteroid dehydrogenase dengan n...

La rabia, o hidrofobia, consiste en una encefalitis aguda, casi invariablemente mortal. Esta zoonosis se presenta en todos los continentes habitados, con excepción de Oceanía, en animales mamíferos que muerden. En Cuba, los más importantes son el perro y el gato, entre los animales domésticos, y la mangosta, entre los salvajes. La enfermedad tiene un periodo de incubación de 2 a 8 semanas. En Cuba se desarrolla un programa de control de la rabia, basado principalmente en medidas epidemiológicas. Con este trabajo pretendemos caracterizar las incidencias de las lesiones por animales, que permitan realizar acciones conjuntas de vigilancia y control de animales, con vistas a disminuir las incidencias de las lesiones por mordeduras.

Breast cancer is one of the most common cancer in the world that occurs in women. Thedevelopment process of cancer is regulated by a variety of pathways that involve various enzymes. COX-2 is an enzyme involved in the inflammatory process in further stages that will play importantroles in breast cancer cells progression. The uses of natural compound from plants give new hope forbreast cancer treatment with minimal side effects. Temulawak is a potential breast cancer drugs because it contains curcuminoid and xanthorizol. Curcumin and xanthorizol has been reported to have chemopreventive effect on colon cancer development. The drug that has same functions of these compounds needed to be examined with various approaches. One of the approach used in this research is molecular docking. Based on ligand analysis with Lipinski and toxicity test using ADMET, curcuminoid and xanthorizol met criteria as medicinal compounds. Curcumin had the highest binding affinity(?G) with the value -9.3 kcal...

Laboratorio del ejército vacuna antirrábica virus rábico Instituto de Higiene Militar r e s u m e n El éxito de la vacuna contra la rabia descubierta por Pasteur contó con una amplia difusión y repercusión por todo el mundo. El hallazgo dio paso a un modelo de ciencia que se materializó en la fundación del Instituto Pasteur, centro que se erigió como el referente internacional para la formación y adquisición del nuevo conocimiento científico. Por este motivo y como ejemplo de transferencia y actualización de las novedades científicas, fueron comisionados dos grupos de facultativos del Cuerpo de Sanidad Militar, uno en 1886 y el siguiente en 1901, para obtener un tratamiento preventivo eficaz contra la rabia que permitiera reducir la morbi-mortalidad de la enfermedad. Unos contactos que arrojaron diversos informes destinados a la evaluación de la implantación de la vacuna antirrábica entre las tropas, y que, junto al análisis de diversas fuentes primarias conservadas en el archivo Militar de Segovia, permiten identificar las principales características que envolvieron a la creación de un laboratorio de elaboración y producción de vacuna de antirrábica en el Instituto de Higiene Militar de Madrid, vigente hasta el último cuarto del siglo XX.

A set of 16 previously synthesized aryl-aminopyridine and aryl-aminoquinoline derivatives have been evaluated for cytotoxic activity against three cancer cell lines (human cervical cancer-HeLa; human chronic myeloid leukemia-K562; human melanoma-Fem-x) and two types of normal peripheral blood mononuclear cells, with and without phytohemaglutinin (PBMC À PHA; PBMC + PHA). Twelve of the studied compounds showed moderate cytotoxicity, with selectivity against K562 but not the remaining two cancer cell lines. Four compounds were not active in cytotoxicity assays, presumably due to high predicted lipophilicity and low solubility. To rationalize the observed cytotoxic effects, structure-based virtual screening was carried out against a pool of potential targets constructed using the inverse docking program Tarfisdock and bibliographical references. The putative targets were identified on the basis of the best correlation between docking scores and in vitro cytotoxicity. It is proposed that the mechanism of action of the studied aminopyridines involves the disruption of signaling pathways and cancer cell cycle through the inhibition of cyclin-dependent kinases and several tyrosine kinases, namely Bcr-Abl kinase and KIT receptor kinase. The obtained results can guide further structural modifications of the studied compounds aimed at developing selective agents targeting proteins involved in cancer cell survival and proliferation.

Somatostatin (growth hormone-inhibiting hormone (GHIH) or somatotropin release-inhibiting factor (SRIF) is recognized as an important mediator and plays great role between the nervous and the immune system along with cancer. Somatostatin (SST) is a hypothalamic, peptide and pancreatic hormone that regulates the endocrine system and cell proliferation via G protein-coupled receptors family. Somatostatin, acting through the 5 somatostatin receptors although the functional role of its receptors (sst(1)-sst(5)) is poorly understood in humans. Despite it consists of thousands of integral membrane proteins exert a wide variety of physiological functions and response to a large portion of the drug targets, but the three dimensional (3D) structure of Somatostatin receptor type 1 [Homo sapiens] has not yet been reported in Protein Data Bank. This is the first report on predicting a three dimensional (3D) structure for Somatostatin receptor type 1 of Homo sapiens. The three dimensional (3D) s...

Objective: A wide range of toxic effects against other species are affected through potential protein molecules called neurotoxins. Among various kinds of toxins, neurotoxins play a critical role in life of other organisms (especially humans). So it is relatively important to know more about neurotoxins and their action on biological systems. All around the world several research works are progressing in the area of neurotoxins. Methods: Here we present NEUROTOX, a database which contains more than 1400 toxin entries originating from more than ~248 different species. The data was enriched with the related data derived from various other protein sequence as well as structural databases and several literature resources. Each entry of toxin contains 18 fields providing detailed information on neurotoxins and their source, fasta formatted protein sequences, molecular weight, toxicity information along with their literature references. Results: In addition, 1086 computationally resolved 3D structures of toxin proteins with validation results were made available for download. Conclusion: The easy to use and freely accessible NEUROTOX database is available online at http: //www. neuro-tox. org and it provides the large range data on toxins.

. Bisphenol-A is one of the Endocrine Disrupting Chemicals (EDCs) found in plastic raw materials, one of which is polycarbonate (PC). BPA is released from the polymer due to the heating process on the packaging, so that the residue accumulates in the body and invades breast cells by controlling the estrogen receptor (ER) and causing breast cancer. Phloroglucinol has the potential to fight the growth of breast cancer cells. This study was conducted to compare the affinity of ERβ to BPA and phloroglucinol using themethod In silico . ERβ macromolecules downloaded from Protein Data Bank (PDB) ( www.rcsb.org ) with code (PDB ID: 3OLS). 2D structures of BPA and phloroglucinol were drawn using the program ChemBioDraw 2D 15.0 and optimized into a 3D structure using the program ChemBioDraw 3D 15.0. BPA and phloroglucinol bedocking to ERβ using program MGLTools 1.5.6 incorporates AutodockTools 4.2.6. The results docking showed the value of the free energy (∆G) of phloroglucinol against ERβ -4...

Structure comparison and alignment are of fundamental importance in structural biology studies. We developed the first universal platform, US-align, to uniformly align monomer and complex structures of different macromolecules (proteins, RNAs, and DNAs). The pipeline is built on a uniform TM-score objective function coupled with a heuristic alignment searching algorithm. Large-scale benchmarks demonstrated significant advantages of US-align over state-of-the-art methods in pairwise and multiple structure alignments of different molecules. Detailed analyses showed that the major advantage of US-align lies in the extensive optimization of the unified objective function powered by efficient heuristic search iterations, which significantly improve the accuracy and speed of the structural alignment process. Meanwhile, the universal protocol fusing different molecular and structural types helps facilitate the heterogeneous oligomer structure comparison and template-based protein-protein and protein-RNA/DNA docking.

Development of new drugs is a time-taking and expensive process. Comprehensive efforts are being made globally toward the search of therapeutics against SARS-CoV-2. Several drugs such as remdesivir, favipiravir, ritonavir, and lopinavir have been included in the treatment regimen and shown effective results in several cases. Among the existing broadspectrum antiviral drugs, remdesivir is found to be more effective against SARS-CoV-2. Remdesivir has broad-spectrum antiviral action against many single-stranded RNA viruses including pathogenic SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). In this study, we proposed that remdesivir strongly binds to membrane protein (Mprotein), RNA-dependent RNA polymerase (RDRP), and main protease (Mprotease) of SARS-CoV-2. It might show antiviral activity by inhibiting more than one target. It has been found that remdesivir binds to Mprotease, Mprotein, and RDRP with −7.8, −7.4, and −7.1 kcal/mol, respectively. The structure dynamics study suggested that binding of remdesivir leads to unfolding of RDRP. It has been found that strong binding of remdesivir to Mprotein leads to decrease in structural deviations and gyrations. Additionally, the average solvent-accessible surface area of Mprotein decreases from 127.17 to 112.12 nm 2 , respectively. Furthermore, the eigenvalues and the trace of the covariance matrix were found to be low in case of Mprotease-remdesivir, Mprotein-remdesivir, and RDRP-remdesivir. Binding of remdesivir to Mprotease, Mprotein, and RDRP reduces the average motions in protein due to its strong binding. The MMPBSA calculations also suggested that remdesivir has strong binding affinity with Mprotein, Mprotease, and RDRP. The detailed analysis suggested that remdesivir has more than one target of SARS-CoV-2.

Determination of the three dimensional (3D) structure of a protein can provide important details about its biological functions and mechanism of action. However, despite their significance, the precise threedimensional structures of most of the proteins are not fully determined till date. The main focus of the current review article is to gain a better understanding of the structural features of the proteins using computational techniques, and their relationship with function. Protein modeling and design is the method aimed to fold a primary amino acids sequence into protein structure with the ultimate goal of designing novel function and behavior. Moreover, proteins can also be designed from scratch or by similarity with the known protein structure. In the current article we have tried to cover various computer aided protein modeling and designing via homology and ab initio modeling, folding study using Molecular Dynamics (MD) methods and in silico mutation analysis.

Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of SARS-CoV-2 Mprotease. It has been found that psilacetin, psilocin, and psilocybine bind to Mprotease with −6.0, −5.4, and −5.8 kcal/mol, respectively. Additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. The binding of psilacetin to Mprotease of SARS-CoV-2 and human interleukin-6 receptors changes the structural dynamics and Gibbs free energy patterns of proteins. These results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for SARS-CoV-2.

The remarkable rise of the current COVID-19 pandemic to every part of the globe has raised key concerns for the current public healthcare system. The spike (S) protein of SARS-CoV-2 shows an important part in the cell membrane fusion and receptor recognition. It is a key target for vaccine production. Several researchers studied the nature of this protein under various environmental conditions. In this work, we applied molecular modeling and extensive molecular dynamics simulation approaches at 0°C (273.15 K), 20°C (293.15 K), 40°C (313.15 K), and 60°C (333.15 K) to study the detailed conformational alterations in the SARS-CoV-2 S protein. Our aim is to understand the influence of temperatures on the structure, function, and dynamics of the S protein of SARS-CoV-2. The structural deviations, and atomic and residual fluctuations were least at low (0°C) and high (60°C) temperature. Even the internal residues of the SARS-CoV-2 S protein are not accessible to solvent at high temperature. Furthermore, there was no unfolding of SARS-CoV-2 spike S reported at higher temperature. The most stable conformations of the SARS-CoV-2 S protein were reported at 20°C, but the free energy minimum region of the SARS-CoV-2 S protein was sharper at 40°C than other temperatures. Our findings revealed that higher temperatures have little or no influence on the stability and folding of the SARS-CoV-2 S protein.

Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of SARS-CoV-2 Mprotease. It has been found that psilacetin, psilocin, and psilocybine bind to Mprotease with −6.0, −5.4, and −5.8 kcal/mol, respectively. Additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. The binding of psilacetin to Mprotease of SARS-CoV-2 and human interleukin-6 receptors changes the structural dynamics and Gibbs free energy patterns of proteins. These results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for SARS...

Development of new drugs is a time-taking and expensive process. Comprehensive efforts are being made globally toward the search of therapeutics against SARS-CoV-2. Several drugs such as remdesivir, favipiravir, ritonavir, and lopinavir have been included in the treatment regimen and shown effective results in several cases. Among the existing broad-spectrum antiviral drugs, remdesivir is found to be more effective against SARS-CoV-2. Remdesivir has broad-spectrum antiviral action against many single-stranded RNA viruses including pathogenic SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). In this study, we proposed that remdesivir strongly binds to membrane protein (Mprotein), RNA-dependent RNA polymerase (RDRP), and main protease (Mprotease) of SARS-CoV-2. It might show antiviral activity by inhibiting more than one target. It has been found that remdesivir binds to Mprotease, Mprotein, and RDRP with −7.8, −7.4, and −7.1 kcal/mol, respectively. The structure d...

Sphingosine kinase 1 (SphK1) is a promising therapeutic target against several diseases including mammary cancer. The aim of present work is to identify a potent lead compound against breast cancer using ligand-based virtual screening, molecular docking, MD simulations, and the MMPBSA calculations. The LBVS in molecular and virtual libraries yielded 20,800 hits, which were reduced to 621 by several parameters of drug-likeness, lead-likeness, and PAINS. Furthermore, 55 compounds were selected by ADMET descriptors carried forward for molecular interaction studies with SphK1. The binding energy (DG) of three screened compounds namely ZINC06823429 (-11.36 kcal/mol), ZINC95421501 (-11.29 kcal/mol), and ZINC95421070 (-11.26 kcal/mol) exhibited stronger than standard drug PF-543 (-9.9 kcal/mol). Finally, it was observed that the ZINC06823429 binds tightly to catalytic site of SphK1 and remain stable during MD simulations. This study provides a significant understanding of SphK1 inhibitors that can be used in the development of potential therapeutics against breast cancer.

Determination of the three dimensional (3D) structure of a protein can provide important details about its biological functions and mechanism of action. However, despite their significance, the precise threedimensional structures of most of the proteins are not fully determined till date. The main focus of the current review article is to gain a better understanding of the structural features of the proteins using computational techniques, and their relationship with function. Protein modeling and design is the method aimed to fold a primary amino acids sequence into protein structure with the ultimate goal of designing novel function and behavior. Moreover, proteins can also be designed from scratch or by similarity with the known protein structure. In the current article we have tried to cover various computer aided protein modeling and designing via homology and ab initio modeling, folding study using Molecular Dynamics (MD) methods and in silico mutation analysis.

Chitin synthase is known to be an important enzyme that catalyzes last step of chitin biosynthetic pathway. It causes linear polymerization of chitin from activated UDP-N-acetylglucosamine monomers in manner joined together by β-(1, 4)-linked. Chitin synthases are thus critical enzymes for synthesis of chitin and as well as for growth and development of insects. In this study, physiochemical properties and modeling of chitin synthase enzyme of Drosophilla melanogaster encoded by CS2 gene was analyzed using in silico approach. Various isoforms (isoforms C and D) of chitin synthase from CS2 gene were used in this study. Physiochemical properties such as molecular weight, theoretical isoelectric point, extinction coefficient, aliphatic index, instability index, total number of negatively and positively charged residues and grand average of hydrophathicity were computed. Along with these physiochemical properties cellular localilization, no. of transmembrane helices, other proteins with which these isoforms interact were also depicted using various tools.

The primary challenge in template-free protein structure prediction is controlling the quality of computed tertiary structures, also known as decoys. While research on how to do so is highly active, the main rule of thumb is to generate as many decoys as can be afforded. This rule acknowledges that more decoys increase the likelihood that some will reside near the sought biologicallyactive/native structure. Generating large numbers of decoys imposes time and space costs. These costs percolate down to decoy selection algorithms that need to select from the generated decoys a few sufficiently near-native. In this paper, we evaluate the hypothesis that the generated decoy ensemble can be significantly reduced without sacrificing decoy quality. Evaluation on diverse proteins shows that drastic reductions can be achieved in the number of preserved decoys while retaining the quality of generated decoys via clustering. The presented results suggest that decoy ensemble reduction promises to aid protein structure prediction.