همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

Statistical Investigation on the Occurrence of Liquid-Liquid Phase Separation in Proteins Involved in Neurodegenerative Proteins

نویسندگان :

Pouya Alimohammadi¹ Saeed Emadi² Mahdi Vasighi³

1- Dept. of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran. 2- Dept. of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran. 3- Dept. of Computer Science and Information Technology, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran.

کلمات کلیدی :

Bioinformatics،phase separation،aggregation،amino acid content،amino acid sequence

چکیده :

A considerable number of people are affected by neurodegenerative diseases worldwide annually. Due to the heterogeneous and complex pathological mechanisms, there is still no standard therapy for these really annoying diseases. A common feature among them is protein aggregation, which varies due to the specific protein and/or peptide. Investigations show there might be relationships between amino acid sequences and the occurrence of aggregation. According to amyloid cascade hypothesis the main pathogenic mechanism that occurs in neurodegenerative diseases is the aggregation (i.e., amyloid formation) of a specific kind of protein or peptide in each disease, during which it converts from the native state to the amyloid state by oligomerization and fibrillation pathway. Another mechanism, proposed recently, is through the establishment of separate phase (liquid-liquid phase separation (LLPS)), containing the amyloidogenic peptide or protein. In this work, we have investigated the effects of occurrence of specific amino acids (content) or specific nearest neighbor (sequence) in neurodegenerative peptides and proteins (e.g., beta-amyloid (Aβ42), tau, alpha-synuclein) that might affect the production of a separate phase, through Data mining approaches. We have analyzed sequence-based statistics investigating the occurrence of LLPS in the LLPSv2 database, and on neurodegenerative peptides and proteins. By making use of LLPSv2 database we calculated amino acid (AAC) and dipeptide compositions (DPC). The calculations were based on linear algebra methods such as PCA, LDA, and PLS, as well as statistical methodologies. Our results indicated that specific AACs such as A, L, F, and Y, and DPCs such as KK, VG, GV, and YY were important in the occurrence of LLPS. We then studied DPC in neurodegenerative peptides and proteins. We concluded that electrostatic, hydrophobic, and hydrophilic interactions were the most important physicochemical properties and were frequently involved in the interactions that play crucial roles in the occurrence of LLPS.