ModFlex: Towards Function Focused Protein Modeling

JOURNAL OF MOLECULAR BIOLOGY

卷:433

Article

Sedova, Mayya¹  Jaroszewski, Lukasz¹  Iyer, Mallika²  Li, Zhanwen¹  Godzik, Adam¹ 

[1] Univ Calif Riverside, Sch Med, Biosci Div, Riverside, CA 92521 USA

[2] Sanford Burnham Prebys Med Discovery Inst, Grad Sch Biomed Sci, La Jolla, CA USA

关键词: homology-based modeling;    structure modeling;    structure prediction;    structural flexibility;    functional substates;   

DOI  :  10.1016/j.jmb.2021.166828

来源: Elsevier

【 摘 要 】

There is a wide, and continuously widening, gap between the number of proteins known only by their amino acid sequence versus those structurally characterized by direct experiment. To close this gap, we mostly rely on homology-based inference and modeling to reason about the structures of the uncharacterized proteins by using structures of homologous proteins as templates. With the rapidly growing size of the Protein Data Bank, there are often multiple choices of templates, including multiple sets of coordinates from the same protein. The substantial conformational differences observed between different experimental structures of the same protein often reflect function related structural flexibility. Thus, depending on the questions being asked, using distant homologs, or coordinate sets with lower resolution but solved in the appropriate functional form, as templates may be more informative. The ModFlex server (https://modflex.org/) addresses this seldom mentioned gap in the standard homology modeling approach by providing the user with an interface with multiple options and tools to select the most relevant template and explore the range of structural diversity in the available templates. ModFlex is closely integrated with a range of other programs and servers developed in our group for the analysis and visualization of protein structural flexibility and divergence. (C) 2021 Published by Elsevier Ltd.

【 授权许可】

Free