Publication: Üç farklı durumdaki G proteini alfa altbiriminin üçüncül yapısının benzeşim modellemesi ve moleküler dinamik simülasyonu ile incelenmesi
Abstract
Tez Başlığı : Üç Farklı Durumdaki G Proteini Alfa Altbiriminin Üçüncül Yapısının Benzeşim Modellemesi ve Moleküler Dinamik Simülasyonu ile İncelenmesi Öğrenci Adı, Soyadı : Aydın KARAGÖZ GTP nükleotidi bağlayan proteinler (G proteinleri) hücre sinyal ileti sisteminin önemli bileşenleridir. Bu proteinler G Proteini Eşlikli Reseptörlerle (GPCR) etkileşmektedir. Çok büyük çeşitliliğe sahip ligandlardan birinin bağlanmasıyla uyarılan GPCR, G proteinini etkinleştirmektedir. Büyük bir çeşitliliğe sahip G proteinleri ve GPCR’lar hücre bölünmesi, duyu sistemleri, hormonal süreçler, nörolojik işlevler gibi çok sayıda fizyolojik süreçlerde görev almakta ve bu süreçlerle ilgili hastalıklarla doğrudan ilişkisi bulunmaktadır. Bundan dolayı sinyal ileti sistemi bileşenleri, özellikle GPCR’lar çok sayıda ilacın hedefi konumundadır. G proteini α, β ve γ olarak adlandırılan 3 alt birimden oluşmaktadır. G proteini alfa alt birimi aktif durumdayken GTP, inaktif durumdayken GDP nükleotidi bağlamaktadır. Çeşitli mutasyonlar Go proteininin etkinliğini değiştirmektedir. Go proteini G protein ailesinin bir üyesi olup yaygın olarak merkezi sinir sisteminde bulunmaktadır. Ancak işlevi henüz tam olarak bilinmemektedir. Bu tez çalışması kapsamında R178A mutasyonunun Go proteininin alfa alt biriminin etkinliğini nasıl değiştirdiği incelendi. R178 amino asidine ilişkin mutasyonun çeşitli hastalıklarda görev aldığı bilinmektedir. Dört farklı durumdaki Go alfa alt birimi benzeşim modellemesi ile modellendi. Elde edilen modeller sulu ortamda 100 µs’ye karşılık gelecek uzunlukta moleküler dinamik simülasyona tabi tutuldu. Simülasyonalar sonucunda R178A mutasyonunun GDP bağlı inaktif proteini daha kararsız hale getirdiği ancak paradoksal şekilde GTP bağlı aktif formu daha kararlı hale getirdiği belirlendi. proteinleri, benzeşim modellemesi, moleküler dinamik simülasyon, protein üçüncül yapısı
Thesis Title: Investigating the Tertiary Structure of Alpha Subunit of the G protein in Three Different States Using Homology Modelling and Molecular Dynamics Simulation Author : Aydın KARAGÖZ GTP nucleotide binding proteins (G proteins) are important components of the cell signal transduction system. These proteins interact with G Protein Coupled Receptors (GPCR). GPCR induced by the binding of one of a wide variety of ligands activates the G protein. A wide variety of G proteins and GPCRs are involved in many physiological processes such as cell division, sensory systems, hormonal processes, and neurological functions, and are directly related to diseases related to these processes. Therefore, signal transduction system components, especially GPCRs, are targets of many drugs. The G protein consists of 3 subunits called α, β and γ. In active form, G protein alpha subunit binds GTP while in inactive form, it binds GDP. Various mutations alter the activity of the Go protein. The Go protein is a member of the G protein family and is commonly found in the central nervous system. However, its function is not yet fully known. In this thesis, how the R178A mutation changes the activity of the alpha subunit of the Go protein was investigated. It is known that the mutation of the R178 amino acid is involved in various diseases. The Go alpha subunit in four different states was modeled by homology modelling. The resulting models were subjected to molecular dynamics simulation with a length corresponding to 100 µs in aqueous. As a result of the simulations, it was determined that the R178A mutation made the GDP-bound inactive protein more unstable, but paradoxically made the GTP-bound active form more stable. proteins, homology modelling, molecular dynamics simulation, tertiary structure
Thesis Title: Investigating the Tertiary Structure of Alpha Subunit of the G protein in Three Different States Using Homology Modelling and Molecular Dynamics Simulation Author : Aydın KARAGÖZ GTP nucleotide binding proteins (G proteins) are important components of the cell signal transduction system. These proteins interact with G Protein Coupled Receptors (GPCR). GPCR induced by the binding of one of a wide variety of ligands activates the G protein. A wide variety of G proteins and GPCRs are involved in many physiological processes such as cell division, sensory systems, hormonal processes, and neurological functions, and are directly related to diseases related to these processes. Therefore, signal transduction system components, especially GPCRs, are targets of many drugs. The G protein consists of 3 subunits called α, β and γ. In active form, G protein alpha subunit binds GTP while in inactive form, it binds GDP. Various mutations alter the activity of the Go protein. The Go protein is a member of the G protein family and is commonly found in the central nervous system. However, its function is not yet fully known. In this thesis, how the R178A mutation changes the activity of the alpha subunit of the Go protein was investigated. It is known that the mutation of the R178 amino acid is involved in various diseases. The Go alpha subunit in four different states was modeled by homology modelling. The resulting models were subjected to molecular dynamics simulation with a length corresponding to 100 µs in aqueous. As a result of the simulations, it was determined that the R178A mutation made the GDP-bound inactive protein more unstable, but paradoxically made the GTP-bound active form more stable. proteins, homology modelling, molecular dynamics simulation, tertiary structure