Analysis of collagen and coiled coil mutations

描述（由申请人提供）：计算生物学主要关注球状蛋白;本申请建议开始使用对人类疾病和多态性数据库的计算分析来解决与纤维蛋白相关的问题。最近的研究表明，它可能是可能的预测的基础上的分子结构和序列保守性时，氨基酸取代将是有害的，并导致临床表型。胶原蛋白和卷曲螺旋结构域，纤维蛋白中发现的两个主要图案的错义突变提出了计算分析。假设这些基序的重复序列模式和超螺旋结构将导致观察到的突变在基序内的位置和取代残基的身份方面的偏差，并且整个重复结构域内的突变位置可能与更高级的结构和结合位点有关。将观察到的突变组与基于核苷酸置换率预期的氨基酸置换的整个组装进行比较。还将检查胶原蛋白序列变异可能导致常见疾病（如骨质疏松症）的可能性以及所有观察到的非同义单核苷酸多态性。

DESCRIPTION (provided by applicant): Computational biology has focused primarily on globular proteins; this application proposes to begin addressing questions related to fibrous proteins using computational analysis on human disease and polymorphism databases. Recent studies suggested it may be possible to predict on the basis of molecular structure and sequence conservation when an amino acid replacement will be deleterious and lead to a clinical phenotype. Computational analyses is proposed on missense mutations in collagen and coiled coil domains, two of the major motifs found in fibrous proteins. It is hypothesized that the repeating sequence patterns and superhelical structures of these motifs will result in biasing of the observed mutations in terms of location within the motif and the identity of the substituting residue, and that the location of mutations within the entire repeating domain may relate to higher order structures and binding sites. The set of observed mutations will be compared with the entire assembly of amino acid replacements expected on the basis of the nucleotide substitution rates. The possibility that variations in collagen sequence could confer a propensity to common diseases such as osteoporosis and the set of all observed non-synonymous single nucleotide polymorphisms will also be examined.