Date of Award
5-2013
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Legacy Department
Physics and Astronomy
Committee Chair/Advisor
Alexov, Emil
Committee Member
Ding , Feng
Committee Member
Tewari , Sumanta
Committee Member
Schwartz , Charles
Committee Member
Roche , Philippe
Abstract
Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will result in an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This investigation focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein. This choice is motivated by the fact that missense mutations are frequently found to affect the native function of proteins by altering their structure, interaction and other properties and cause diseases. A particular disease is the Snyder-Robinson syndrome (SRS), which is an X-linked mental retardation found to be caused by missense mutations in human spermine synthase (SMS). In this thesis, a rational approach to predict the effects of missense mutations on SMS wild-type characteristics was carried. Following this work, a structure-based virtual screening of small molecules was applied to rescue the disease-causing effect by searching the small molecules to stabilize the malfunctioning SMS mutant dimer.
Recommended Citation
Zhang, Zhe, "IN SILICO MODELING THE EFFECT OF SINGLE POINT MUTATIONS AND RESCUING THE EFFECT BY SMALL MOLECULES BINDING" (2013). All Dissertations. 1126.
https://tigerprints.clemson.edu/all_dissertations/1126