Clustering Protein Sequences ? Structure Prediction by Transitive Homology

نویسندگان

  • Eva Bolten
  • Alexander Schliep
  • Sebastian Schneckener
  • Dietmar Schomburg
  • Rainer Schrader
چکیده

MOTIVATION It is widely believed that for two proteins Aand Ba sequence identity above some threshold implies structural similarity due to a common evolutionary ancestor. Since this is only a sufficient, but not a necessary condition for structural similarity, the question remains what other criteria can be used to identify remote homologues. Transitivity refers to the concept of deducing a structural similarity between proteins A and C from the existence of a third protein B, such that A and B as well as B and C are homologues, as ascertained if the sequence identity between A and B as well as that between B and C is above the aforementioned threshold. It is not fully understood if transitivity always holds and whether transitivity can be extended ad infinitum. RESULTS We developed a graph-based clustering approach, where transitivity plays a crucial role. We determined all pair-wise similarities for the sequences in the SwissProt database using the Smith-Waterman local alignment algorithm. This data was transformed into a directed graph, where protein sequences constitute vertices. A directed edge was drawn from vertex A to vertex B if the sequences A and B showed similarity, scaled with respect to the self-similarity of A, above a fixed threshold. Transitivity was important in the clustering process, as intermediate sequences were used, limited though by the requirement of having directed paths in both directions between proteins linked over such sequences. The length dependency-implied by the self-similarity-of the scaling of the alignment scores appears to be an effective criterion to avoid clustering errors due to multi-domain proteins. To deal with the resulting large graphs we have developed an efficient library. Methods include the novel graph-based clustering algorithm capable of handling multi-domain proteins and cluster comparison algorithms. Structural Classification of Proteins (SCOP) was used as an evaluation data set for our method, yielding a 24% improvement over pair-wise comparisons in terms of detecting remote homologues. AVAILABILITY The software is available to academic users on request from the authors. CONTACT [email protected]; [email protected]; [email protected]; [email protected]; [email protected]. SUPPLEMENTARY INFORMATION http://www.zaik.uni-koeln.de/~schliep/ProtClust.html.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Protein Secondary Structure Prediction: a Literature Review with Focus on Machine Learning Approaches

DNA sequence, containing all genetic traits is not a functional entity. Instead, it transfers to protein sequences by transcription and translation processes. This protein sequence takes on a 3D structure later, which is a functional unit and can manage biological interactions using the information encoded in DNA. Every life process one can figure is undertaken by proteins with specific functio...

متن کامل

Constructive Induction and Protein Tertiary Structure Prediction

To date, the only methods that have been used successfully to predict protein structures have been based on identifying homologous proteins whose structures are known. However, such methods are limited by the fact that some proteins have similar structure but no significant sequence homology. We consider two ways of applying machine learning to facilitate protein structure prediction. We argue ...

متن کامل

In Silico Prediction and Docking of Tertiary Structure of Multifunctional Protein X of Hepatitis B Virus

Hepatitis B virus (HBV) infection is a universal health problem and may result into acute, fulminant, chronic hepatitis liver cirrhosis, or hepatocellular carcinoma. Sequence for protein X of HBV was retrieved from Uniprot database. ProtParam from ExPAsy server was used to investigate the physicochemical properties of the protein. Homology modeling was carried out using Phyre2 server, and refin...

متن کامل

In silico Prediction and Docking of Tertiary Structure of LuxI, an Inducer Synthase of Vibrio fischeri

Background: LuxI is a component of the quorum sensing signaling pathway in Vibrio fischeri responsible for the inducer synthesis that is essential for bioluminescence. Methods: Homology modeling of LuxI was carried out using Phyre2 and refined with the GalaxyWEB server. Five models were generated and evaluated by ERRAT, ANOLEA, QMEAN6, and Procheck. Results: Five refined models were gener...

متن کامل

In Silico and in Vitroinvestigations on cry4aand cry11atoxins of Bacillus thuringiensis var Israelensis

In the present study we attempted to correlate the structure and function of the cry11a (72 kDa) and cry4a (135 kDa) proteins of Bacillus thuringiensis var israelensis. Homology modeling and secondary structure predictions were done to locate most probable regions for finding helices or strands in these proteins. The JPRED (JPRED consensus secondary structure prediction server) secondary struct...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Bioinformatics

دوره 17 10  شماره 

صفحات  -

تاریخ انتشار 1999