• Genomics & Informatics
• /
• v.20 no.2
• /
• pp.24.1-24.8
• /
• 2022

Hypomyelinating leukodystrophy type 2 (HLD2), is an inherited genetic disease of the central nervous system caused by recessive mutations in the gap junction protein gamma 2 (GJC2/GJA12). HLD2 is characterized by nystagmus, developmental delay, motor impairments, ataxia, severe speech problem, and hypomyelination in the brain. The GJC2 sequence encodes connexin 47 protein (Cx47). Connexins are a group of membrane proteins that oligomerize to construct gap junctions protein. In the present study, a novel missense mutation gene c.760G>A (p.Val254Met) was identified in a patient with HLD2 by performing whole exome sequencing. Following the discovery of the new mutation in the proband, we used Sanger sequencing to analyze his affected sibling and parents. Sanger sequencing verified homozygosity of the mutation in the proband and his affected sibling. The autosomal recessive inheritance pattern was confirmed since Sanger sequencing revealed both healthy parents were heterozygous for the mutation. PolyPhen2, SIFT, PROVEAN, and CADD were used to evaluate the function prediction scores of detected mutations. Cx47 is essential for oligodendrocyte function, including adequate myelination and myelin maintenance in humans. Novel mutation p.Val254Met is located in the second extracellular domain of Cx47, both extracellular loops are highly conserved and probably induce intramolecular disulfide interactions. This novel mutation in the Cx47 gene causes oligodendrocyte dysfunction and HLD2 disorder.

• Journal of Integrative Natural Science
• /
• v.3 no.1
• /
• pp.49-53
• /
• 2010

Molecular docking is a critical event which mostly forms Van der waals complex in molecular recognition. Since the majority of developed drugs are small molecules, docking them into proteins has been a prime concern in drug discovery community. Since the binding pose space is too vast to cover completely, many search algorithms such as genetic algorithm, Monte Carlo, simulated annealing, distance geometry have been developed. Proper evaluation of the quality of binding is an essential problem. Scoring functions derived from force fields handle the ligand binding prediction with the use of potential energies and sometimes in combination with solvation and entropy contributions. Knowledge-based scoring functions are based on atom pair potentials derived from structural databases. Forces and potentials are collected from known protein-ligand complexes to get a score for their binding affinities (e.g. PME). Empirical scoring functions are derived from training sets of protein-ligand complexes with determined affinity data. Because non of any single scoring function performs generally better than others, some other approaches have been tried. Although numerous scoring functions have been developed to locate the correct binding poses, it still remains a major hurdle to derive an accurate scoring function for general targets. Recently, consensus scoring functions and target specific scoring functions have been studied to overcome the current limitations.

• Journal of IKEEE
• /
• v.13 no.3
• /
• pp.18-23
• /
• 2009

FEATURE is a computational method to recognize functional and structural sites for automatic protein function prediction. By profiling physicochemical properties around residues, FEATURE can characterize and predict functional and structural sites in 3D protein structures in a high-throughput manner. Despite its effectiveness, it has been challenging to apply FEATURE to novel protein data due to limited customization support. To address this problem, we thoroughly analyze the internal modules of FEATURE and propose a methodology to customize FEATURE so that it can be used for new protein data for automatic functional annotations.

• The KIPS Transactions:PartD
• /
• v.8D no.5
• /
• pp.553-560
• /
• 2001

Bioinformatics is a discipline to support biological experiment projects by storing, managing data arising from genome research. In can also lead the experimental design for genome function prediction and regulation. Among various approaches of the genome research, the proteomics have been drawing increasing attention since it deals with the final product of genomes, i.e., proteins, directly. This paper proposes a data mining technique to predict the structural characteristics of a given protein group, one of dominant factors of the functions of them. After explains associations among amino acid subsequences in the primary structures of proteins, which can provide important clues for determining secondary or tertiary structures of them, it defines a sequence association rule to represent the inter-subsequences. It also provides support and confidence measures, newly designed to evaluate the usefulness of sequence association rules, After is proposes a method to discover useful sequence association rules from a given protein group, it evaluates the performance of the proposed method with protein sequence data from the SWISS-PROT protein database.

• The KIPS Transactions:PartD
• /
• v.11D no.4
• /
• pp.845-854
• /
• 2004

Motif databases are used in the function and structure prediction of proteins. The frequency of use about these databases increases continuously because of protein sequence data growth. Recently, many researches about motif resource integration are proceeding. However, existing motif databases were developed independently, thus these databases have a heterogeneous search result problem. Database intnegration for this problem resolution has a periodic update problem, a complex query process problem, a duplicate database entry handling problem and BML support problem. Therefore, in this paper, we suppose a database resource integration method for these problem resolution, describe periodically integrated database update method and XML transformation. finally, we estimate the implementation of our prototype and a case database.

• Proceedings of the Korean Society for Bioinformatics Conference
• /
• 2003.10a
• /
• pp.26-51
• /
• 2003

Large scale protein interaction maps provide a new, global perspective with which to analyse protein function. PSIMAP, the Protein Structural Interactome Map, is a database of all the structurally observed interactions between superfamilies of protein domains with known three-dimensional structure in thePDB. PSIMAP incorporates both functional and evolutionary information into a single network. It makes it possible to age protein domains in terms of taxonomic diversity, interaction and function. One consequence of it is to predict the most important protein domain structure in evolution. We present a global analysis of PSIMAP using several distinct network measures relating to centrality, interactivity, fault-tolerance, and taxonomic diversity. We found the following results: ${\bullet}$ Centrality: we show that the center and barycenter of PSIMAP do not coincide, and that the superfamilies forming the barycenter relate to very general functions, while those constituting the center relate to enzymatic activity. ${\bullet}$ Interactivity: we identify the P-loop and immunoglobulin superfamilies as the most highly interactive. We successfully use connectivity and cluster index, which characterise the connectivity of a superfamily's neighbourhood, to discover superfamilies of complex I and II. This is particularly significant as the structure of complex I is not yet solved. ${\bullet}$ Taxonomic diversity: we found that highly interactive superfamilies are in general taxonomically very diverse and are thus amongst the oldest. This led to the prediction of the oldest and most important protein domain in evolution of lift. ${\bullet}$ Fault-tolerance: we found that the network is very robust as for the majority of superfamilies removal from the network will not break up the network. Overall, we can single out the P-loop containing nucleotide triphosphate hydrolases superfamily as it is the most highly connected and has the highest taxonomic diversity. In addition, this superfamily has the highest interaction rank, is the barycenter of the network (it has the shortest average path to every other superfamily in the network), and is an articulation vertex, whose removal will disconnect the network. More generally, we conclude that the graph-theoretic and taxonomic analysis of PSIMAP is an important step towards the understanding of protein function and could be an important tool for tracing the evolution of life at the molecular level.

• Journal of the Korea Society of Computer and Information
• /
• v.14 no.1
• /
• pp.73-80
• /
• 2009

G protein-coupled receptors(GPCRs) family is a cell membrane protein, and plays an important role in a signaling mechanism which transmits external signals through cell membranes into cells. But, GPCRs each are known to have various complex control mechanisms and very unique signaling mechanisms. Structural features, and family and subfamily of GPCRs are well known by function. and accordingly, the most fundamental work in studies identifying the previous GPCRs is to classify the GPCRs with given protein sequences. Studies for classifying previously identified GPCRs more easily with mathematical models have been mainly going on. In this paper Considering that functions of proteins are determined by their stereoscopic structures, the present paper proposes a method to compare secondary structures of two GPCRs having different amino acid sequences, and then detect an unknown GPCRs assumed to have a same function in databases of previously identified GPCRs.

• Proceedings of the Korean Information Science Society Conference
• /
• 2004.10b
• /
• pp.286-288
• /
• 2004

단백질 상호작용 데이터는 현 생물정보학에서 기능이 알려지지 않은 단백질의 기능 예측에 높은 신뢰성이 있는 프로티오믹스의 계산 모델에 이용되고 있다. 일반적으로 이 단백질 기능 예측 알고리즘들은 대규모의 2차원 단백질-단백질 상호작용 맵에서 Guilt-by-Association 개념 기반으로 개발되고 있다. 본 논문에서는 단백질-단백질 상호작용 데이터를 이용한 그래프 기반 단백질 기능 예측 모델을 개발하였다. 특히, 이 모델은 대량의 상호작용 데이터에서 정확한 기능 예측을 수행할 수 있다는 장점을 가지고 있다. 이를 위해 Yeast에 대한 단백질 상호작용 맵, Homology 및 Interaction Generality를 이용하여 이 모델을 평가하였다.

• Proceedings of the Korean Information Science Society Conference
• /
• 2005.11b
• /
• pp.238-240
• /
• 2005

단백체는 세포가 처해있는 환경에 따라, 그리고 각 조직 별로 유동적으로 존재하며, 세포의 실제적인 기능을 표현해준다. 이러한 이유로 세포 내에서 일어나는 실제적인 현상들을 전체 단백질 단계에서 통합적으로 파악하고자 하는 단백체학 연구가 활발하게 진행되고 있다. 미지의 단백질의 기능을 밝혀내는 연구는 단백체학의 가장 기본적이면서 중요한 부분이라고 할 수 있다. 본 논문에서는 "단백질 상호작용 네트웍 사전(PIND)"을 구축함으로써 단백질의 기능을 예측하는 새로운 방법론을 소개한다.

• Journal of the Korea Institute of Information and Communication Engineering
• /
• v.22 no.1
• /
• pp.26-32
• /
• 2018

The protein secondary structures are important information for studying the evolution, structure and function of proteins. Recently, deep learning methods have been actively applied to predict the secondary structure of proteins using only protein sequence information. In these methods, widely used input features are protein profiles transformed from protein sequences. In this paper, to obtain an effective protein profiles, protein profiles were constructed using protein sequence search methods such as PSI-BLAST and HHblits. We adjust the similarity threshold for determining the homologous protein sequence used in constructing the protein profile and the number of iterations of the profile construction using the homologous sequence information. We used the protein profiles as inputs to convolutional neural networks and recurrent neural networks to predict the secondary structures. The protein profile that was created by adding evolutionary information only once was effective.