Molecular Characterization of HOXA2 and HOXA3 Binding Properties

From MDPI via Jisc Publications RouterHistory: accepted 2021-11-30, pub-electronic 2021-12-03Publication status: PublishedFunder: SPARC (Scheme for Promotion of Academic and Research Collaboration) and UKIERI (United Kingdom India Research Initiative); Grant(s): project P657Funder: Biotechnology and Biological Sciences Research Council; Grant(s): BB/N00907X/1 and BB/T007761/1The highly conserved HOX homeodomain (HD) transcription factors (TFs) establish the identity of different body parts along the antero−posterior axis of bilaterian animals. Segment diversification and the morphogenesis of different structures is achieved by generating precise patterns of HOX expression along the antero−posterior axis and by the ability of different HOX TFs to instruct unique and specific transcriptional programs. However, HOX binding properties in vitro, characterised by the recognition of similar AT-rich binding sequences, do not account for the ability of different HOX to instruct segment-specific transcriptional programs. To address this problem, we previously compared HOXA2 and HOXA3 binding in vivo. Here, we explore if sequence motif enrichments observed in vivo are explained by binding affinities in vitro. Unexpectedly, we found that the highest enriched motif in HOXA2 peaks was not recognised by HOXA2 in vitro, highlighting the importance of investigating HOX binding in its physiological context. We also report the ability of HOXA2 and HOXA3 to heterodimerise, which may have functional consequences for the HOX patterning function in vivo

Global network of computational biology communities: ISCB's regional student groups breaking barriers [version 1; peer review: Not peer reviewed]

Regional Student Groups (RSGs) of the International Society for Computational Biology Student Council (ISCB-SC) have been instrumental to connect computational biologists globally and to create more awareness about bioinformatics education. This article highlights the initiatives carried out by the RSGs both nationally and internationally to strengthen the present and future of the bioinformatics community. Moreover, we discuss the future directions the organization will take and the challenges to advance further in the ISCB-SC main mission: “Nurture the new generation of computational biologists”.Fil: Shome, Sayane. University of Iowa; Estados UnidosFil: Parra, Rodrigo Gonzalo. European Molecular Biology Laboratory; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fatima, Nazeefa. Uppsala Universitet; SueciaFil: Monzon, Alexander Miguel. Università di Padova; ItaliaFil: Cuypers, Bart. Universiteit Antwerp; BélgicaFil: Moosa, Yumna. University of KwaZulu Natal; SudáfricaFil: Da Rocha Coimbra, Nilson. Universidade Federal de Minas Gerais; BrasilFil: Assis, Juliana. Universidade Federal de Minas Gerais; BrasilFil: Giner Delgado, Carla. Universitat Autònoma de Barcelona; EspañaFil: Dönertaş, Handan Melike. European Molecular Biology Laboratory. European Bioinformatics Institute; Reino UnidoFil: Cuesta Astroz, Yesid. Universidad de Antioquia; Colombia. Universidad Ces. Facultad de Medicina.; ColombiaFil: Saarunya, Geetha. University of South Carolina; Estados UnidosFil: Allali, Imane. Universite Mohammed V. Rabat; Otros paises de África. University of Cape Town; SudáfricaFil: Gupta, Shruti. Jawaharlal Nehru University; IndiaFil: Srivastava, Ambuj. Indian Institute of Technology Madras; IndiaFil: Kalsan, Manisha. Jawaharlal Nehru University; IndiaFil: Valdivia, Catalina. Universidad Andrés Bello; ChileFil: Olguín Orellana, Gabriel José. Universidad de Talca; ChileFil: Papadimitriou, Sofia. Vrije Unviversiteit Brussel; Bélgica. Université Libre de Bruxelles; BélgicaFil: Parisi, Daniele. Katholikie Universiteit Leuven; BélgicaFil: Kristensen, Nikolaj Pagh. Technical University of Denmark; DinamarcaFil: Rib, Leonor. Universidad de Copenhagen; DinamarcaFil: Guebila, Marouen Ben. University of Luxembourg; LuxemburgoFil: Bauer, Eugen. University of Luxembourg; LuxemburgoFil: Zaffaroni, Gaia. University of Luxembourg; LuxemburgoFil: Bekkar, Amel. Universite de Lausanne; SuizaFil: Ashano, Efejiro. APIN Public Health Initiatives; NigeriaFil: Paladin, Lisanna. Università di Padova; ItaliaFil: Necci, Marco. Università di Padova; ItaliaFil: Moreyra, Nicolás Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentin

A novel peptide thrombopoietin mimetic designing and optimization using computational approach

Thrombopoietin receptor (TPOR) is a cytokine receptor protein; activation of cell surface TPOR by thrombopoietin (TPO) triggers an intracellular cascade of megakaryocytopoiesis for the formation of platelets. TPO is a glycoprotein hormone which stimulates megakaryocytes formation and maturation to platelets in bone marrow. Ex vivo megakaryocytopoiesis is in highlight for its vast role in therapeutics and field of regenerative medicine. For therapeutic uses, various TPO alternatives have been used however they are associated with issues like recombinant TPO administration is associated with the generation of auto antibodies and its production is an expensive process. Moreover, reported thrombopoietin mimetic peptide (TMP) has no sequence homology with TPO and low specificity to TPOR. Hence, in this study, a novel peptidic TPO mimetic is designed through computational studies by studying the binding sites of TPO and TMP to TPOR and analogs of known mimetics. Screening of combinatorial library was done through molecular docking using ClusPro and mimetic-9 was found to have better binding score of -938.8 kcal/mol with seven hydrogen bonds and a high number of hydrophobic interactions, than known mimetic TMP with docking score of -798.4 kcal/mol and TMP dimer with docking score of -811.9 kcal/mol for TPOR. Mimetic-9 interaction with TPOR was further assessed by the molecular dynamics simulation and their complex was found to be stable with an RMSD value of 0.091 Aº. Resulting mimetic-9 was found to have overall good physiochemical properties with positive grand average hydropathy (GRAVY) score and high instability index score and it was found to be localized in the extracellular region. The designed mimetic-9 might prove to be a useful lead molecule for mimicking the role of TPO and to help for platelet production in vitro with higher efficiency

Molecular Characterization of HOXA2 and HOXA3 Binding Properties

The highly conserved HOX homeodomain (HD) transcription factors (TFs) establish the identity of different body parts along the antero–posterior axis of bilaterian animals. Segment diversification and the morphogenesis of different structures is achieved by generating precise patterns of HOX expression along the antero–posterior axis and by the ability of different HOX TFs to instruct unique and specific transcriptional programs. However, HOX binding properties in vitro, characterised by the recognition of similar AT-rich binding sequences, do not account for the ability of different HOX to instruct segment-specific transcriptional programs. To address this problem, we previously compared HOXA2 and HOXA3 binding in vivo. Here, we explore if sequence motif enrichments observed in vivo are explained by binding affinities in vitro. Unexpectedly, we found that the highest enriched motif in HOXA2 peaks was not recognised by HOXA2 in vitro, highlighting the importance of investigating HOX binding in its physiological context. We also report the ability of HOXA2 and HOXA3 to heterodimerise, which may have functional consequences for the HOX patterning function in vivo

Global network of computational biology communities : ISCB's regional student groups breaking barriers [version 1; peer review: Not peer reviewed]

Regional Student Groups (RSGs) of the International Society for Computational Biology Student Council (ISCB-SC) have been instrumental to connect computational biologists globally and to create more awareness about bioinformatics education. This article highlights the initiatives carried out by the RSGs both nationally and internationally to strengthen the present and future of the bioinformatics community. Moreover, we discuss the future directions the organization will take and the challenges to advance further in the ISCB-SC main mission: "Nurture the new generation of computational biologists"

Global network of computational biology communities

Regional Student Groups (RSGs) of the International Society for Computational Biology Student Council (ISCB-SC) have been instrumental to connect computational biologists globally and to create more awareness about bioinformatics education. This article highlights the initiatives carried out by the RSGs both nationally and internationally to strengthen the present and future of the bioinformatics community. Moreover, we discuss the future directions the organization will take and the challenges to advance further in the ISCB-SC main mission: “Nurture the new generation of computational biologists”.PubMedScopu