한빛사 논문
Hahnbeom Park1, Gyu Rie Lee1, David E. Kim1,2, Ivan Anishchenko1, Qian Cong1, David Baker1,2,*
1 Department of Biochemistry and Institute forProtein Design, University of Washington, Seattle, Washington
2 Howard Hughes Medical Institute, Universityof Washington, Seattle, Washington
*Correspondence : David Baker, Howard Hughes MedicalInstitute, University of Washington,Seattle, WA.
Abstract
Because proteins generally fold to their lowest free energy states, energy‐guided refinement in principle should be able to systematically improve the quality of protein structure models generated using homologous structure or co‐evolution derived information. However, because of the high dimensionality of the search space, there are far more ways to degrade the quality of a near native model than to improve it, and hence, refinement methods are very sensitive to energy function errors. In the 13th Critial Assessment of techniques for protein Structure Prediction (CASP13), we sought to carry out a thorough search for low energy states in the neighborhood of a starting model using restraints to avoid straying too far. The approach was reasonably successful in improving both regions largely incorrect in the starting models as well as core regions that started out closer to the correct structure. Models with GDT‐HA over 70 were obtained for five targets and for one of those, an accuracy of 0.5 å backbone root‐mean‐square deviation (RMSD) was achieved. An important current challenge is to improve performance in refining oligomers and larger proteins, for which the search problem remains extremely difficult.
Keywords : energy function, homology modeling, protein conformational search, rotein structure prediction
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