Molecular modeling of soluble proteins

可溶性蛋白质的分子建模

• 批准号: 8349654
• 负责人: Stefano Costanzi
• 金额: $ 8.02万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8349654
• 关键词: 3-Dimensional; Antineoplastic Agents; Antiviral Agents; Bioinformatics; Biological; Collaborations; Computer Assisted; Computing Methodologies; Cytarabine; Cytidine; Cytidine Deaminase; Cytidine Deaminase Inhibitor; Databases; Deamination; Development; Discipline; Docking; Enzymes; Evaluation; G-Protein-Coupled Receptors; Homology Modeling; Human; Italy; Lead; Ligands; Molecular; Molecular Models; Molecular Weight; Nucleotides; Pharmaceutical Preparations; Pharmacologic Substance; Phylogenetic Analysis; Proteins; Publishing; Quantitative Structure-Activity Relationship; Research; Resources; Screening procedure; Structure-Activity Relationship; System; Techniques; Testing; Time; Universities; Uridine; Work; base; cheminformatics; drug discovery; extracellular; improved; interest; leukemia; molecular dynamics; molecular modeling; novel; virtual

In the course of this fiscal year, we have worked on the soluble systems described in the following paragraphs, which constitute attractive targets for the development of pharmaceutical agents. Human cytidine deaminase (CDA). Cytidine deaminase (CDA) is a cytosolic enzyme which catalyzes the hydrolytic deamination of cytidine to uridine. CDA causes also the degradation of several cytidine based compounds potentially active as anticancer or antiviral agents, including the anti-leukemic agent cytosine arabinoside (AraC). In particular, during this fiscal year, we have conducted the research and accomplished the results described in the following paragraphs. 1) Finalized and published a virtual screening for the identification of CDA inhibitors. This work led to the identification of several active compounds, potentially developable into new pharmacological agents for the treatment of leukemia. Moreover, it significantly advanced the current understanding of the molecular mechanisms of nucleotide recognition by CDA. Experimental collaborators: Prof. Alberto Vita and Prof. Silvia Vincenzetti (University of Camerino, Italy). 2) Continued the studies for the identification of novel drug-like CDA inhibitors. Experimental collaborators: Prof. Alberto Vita and Prof. Silvia Vincenzetti (University of Camerino, Italy).

在本财政年度期间，我们致力于以下段落所述的可溶性系统，这些系统构成了药物开发的诱人目标。 人胞苷脱氨酶（CDA）。胞苷脱氨酶（CDA）是一种胞质酶，催化胞苷水解脱氨为尿苷。CDA还引起几种基于胞苷的化合物的降解，这些化合物可能具有抗癌或抗病毒剂的活性，包括抗白血病剂阿糖胞苷（AraC）。 特别是在本财政年度，我们进行了研究，并取得了以下段落所述的成果。 1)完成并发布了一个用于鉴定CDA抑制剂的虚拟筛选。这项工作导致了几种活性化合物的鉴定，这些化合物可能会发展成为治疗白血病的新药物。此外，它显着推进了目前的核苷酸识别的分子机制的CDA的理解。实验合作者：Alberto Vita教授和Silvia Pirenzetti教授（卡梅里诺大学，意大利）。 2)继续进行新药样CDA抑制剂的鉴定研究。实验合作者：Alberto Vita教授和Silvia Pirenzetti教授（卡梅里诺大学，意大利）。

项目成果

Prediction of passive blood-brain partitioning: straightforward and effective classification models based on in silico derived physicochemical descriptors.

• DOI: 10.1016/j.jmgm.2010.03.010
• 发表时间: 2010-06
• 期刊: JOURNAL OF MOLECULAR GRAPHICS & MODELLING
• 影响因子: 2.9
• 作者: Vilar, Santiago;Chakrabarti, Mayukh;Costanzi, Stefano
• 通讯作者: Costanzi, Stefano

Role of tyrosine 33 residue for the stabilization of the tetrameric structure of human cytidine deaminase.

• DOI: 10.1016/j.ijbiomac.2010.07.001
• 发表时间: 2010-11-01
• 期刊: International journal of biological macromolecules
• 影响因子: 8.2
• 作者: Micozzi D;Pucciarelli S;Carpi FM;Costanzi S;De Sanctis G;Polzonetti V;Natalini P;Santarelli IF;Vita A;Vincenzetti S
• 通讯作者: Vincenzetti S

Delineation of the molecular mechanisms of nucleoside recognition by cytidine deaminase through virtual screening.

• DOI: 10.1002/cmdc.201100139
• 发表时间: 2011-08-01
• 期刊: CHEMMEDCHEM
• 影响因子: 3.4
• 作者: Costanzi, Stefano;Vilar, Santiago;Micozzi, Daniela;Carpi, Francesco M.;Ferino, Giulio;Vita, Alberto;Vincenzetti, Silvia
• 通讯作者: Vincenzetti, Silvia