A novel strategy to determine protein structures using exclusively residual dipolar coupling

作者：Rathinavelan Thenmalarchelvi; Im Wonpil^*

来源：Journal of Computational Chemistry, 2008, 29(10): 1640-1649.

DOI：10.1002/jcc.20923

• singular value decomposition
• replica exchange
• torsion angle molecular dynamics
• fragment superposition method
• protein G

Recent advances in NMR techniques to measure anisotropic spin interactions such as residual dipolar coupling (RDC) have provided better insights into protein structure as well as dynamics. Exploitation of RDC, however, still remains challenging because its successful application requires a reasonable starting model. Using the singular value decomposition method, we have recently developed an RDC restraint potential to optimally extract orientational information from RDC without the prerequisite of any structural information. In the present study, its efficacy is further illustrated by folding a beta-hairpin and alpha-helix of protein G from extended conformations with RDC restraints alone by employing the replica exchange torsion angle molecular dynamics (REX-TAMD) technique. Subsequently, the entire structure of protein G has been determined accurately using the developed fragment superposition method (FRAGSUM). In FRAGSUM, each overlapping fragments (10 amino acids long) is first folded individually by REX-TAMD, and then the common amino acids are superimposed to determine the entire structure. Because FRAGSUM does not require any additional information besides RDC, it offers a new strategy for de novo structure determination using exclusively RDC.

• 出版日期2008-7-30
• 单位上海生物信息技术研究中心