ABSTRACT
Background: Hyperemesis Gravidarum (HG) is acommon pregnancy complication that occurs in0.3–2% of pregnancies. Growth/Differentiation Factor(GDF) 15 serum levels are abnormally high in patientsassociated with HG. In silico analysis providesinformation about structure and function of GDF15.Aim and Objectives: The aim of this study was to enlistbiochemical and functional properties of GDF15protein and determine its three-dimensional structure,as GDF15 is known to be associated with risk of HG.Material and Methods: The PDB file of GDF15[NP_004855] was created by RaptorX structureprediction server. The UCLA-DOE server was used tovisual analysis of crystal structure of protein. Thevalidation for structure models was performed by usingPROCHECK. Model quality estimates were based onthe QMEAN and ProSA. Results: The model showedgood stereo-chemical property in terms of G-factorvalue -0.64, that indicates geometry of modelcorresponds to probability conformation with 95%residue in the favored region of Ramachandran plot,showing high accuracy of model prediction. The Zscore of -4.04 predicted by ProSA represents the goodquality of the model. The energy plot shows the localmodel quality by plotting knowledge-based energies asa function of amino acid sequence position.Conclusion: The generated model could be supportiveto understand the structure and functionalcharacteristics of Homo sapiens growth/differentiationfactor 15 [NP_004855]. As abnormal high serum levelsof GDF15 were observe in patients associated with HG.Therefore, the structure model of GDF15 [NP_004855]is useful to understand its role in development of HG. InSilico docking study could be explain the molecularassociation of GDF15 [NP_004855] with HG and newdrug designing, for that structure model is very useful.
ABSTRACT
Objetivo. Construir un modelo molecular teórico de la estructura terciara del receptor 5HT2A de Homo sapiens a partir de estructurasobtenidas experimentalmente como plantillas. Materiales y métodos. Para la realización del modelo teórico se contempló el protocoloestablecido por Ballesteros y Weinstein para la construcción del receptor acoplado proteína G, por medio de alineamiento de la secuenciade aminoácidos, perfiles de hidrofobicidad, refinamiento de bucles por restricciones espaciales, y minimización de energía con el campode fuerza OPLS_2005. Resultados. El modelo obtenido fue validado por el gráfico de Ramachandran con un 91,7% de aminoácidosdentro de los límites establecidos para ángulos phi y psi, y un RMSD de 0,95 Å con respecto a rodopsina de bovino. Conclusiones. Seobtuvo un modelo teórico validado, útil para realización de estudios de acoplamiento ligando-receptor...
Objective Build a theoretical molecularmodel of the tertiary structure of the Homo sapiens 5HT2A receptor from experimentally obtained structures as templates. Materialsand methods In the construction of the theoretical model we considered the protocol established by Ballesteros and Weinstein for theconstruction of the G-protein coupled receptor, by the alignment of the amino acid sequence, hydrophobicity profiles, refinement ofloops by spatial restrictions and energy minimization with the force field OPLS_2005. Results The resulting model was validated bythe Ramachandran plot with 91.7% of amino acids within the limits set for angles phi and psi and a RMSD of 0.95 Å with respect tobovine rhodopsin. Conclusions We obtained a validated theoretical model useful in studies of ligand-receptor docking...
Objetivo. Construir um modelo molecularteórico da estrutura terciária do receptor 5HT2A de Homo Sapiens, com estruturas obtidas experimentalmente como moldes. Materiaise métodos. Para a elaboração do modelo teórico se utilizou o protocolo estabelecido por Ballesteros e Weinstein para a construção doreceptor acoplado à proteína G, por intermédio de alinhamento da seqüência de aminoácidos, perfis de hidrofobicidade, refinamento debucles por restrições espaciais e minimização da energia com o campo de força OPLS_2005. Resultados. O modelo obtido foi validadopelo gráfico de Ramachandran com 91,7% dos aminoácidos dentro dos limites estabelecidos para os ângulos phi e psi, e um RMSD de0,95 Å com respeito à rodopsina de bovino. Conclusões. Obteve-se um modelo teórico validado, útil para a realização de estudos deacoplamento ligante-receptor...