Journal
PROTEIN SCIENCE
Volume 25, Issue 1, Pages 255-269Publisher
WILEY
DOI: 10.1002/pro.2751
Keywords
protein folding; binding; protein-protein interactions; energy landscape theory; long-range electrostatics; Debye-Huckel potentials; electrostatically induced frustration
Categories
Funding
- Center for Theoretical Biological Physics (CTBP), NSF [PHY-1308264, PHY-1427654]
- Ministry of Science and Technology (MOST), Taiwan, R.O.C. [103-2917-I-564-015]
- NIH National Institute of General Medical Sciences [P01-GM071862, R01-GM044557]
- D.R. Bullard-Welch Chair at Rice University [C-0016]
- NSF [MCB 1412532]
- D.O.E [DE-FG02-10ER16175]
- Direct For Mathematical & Physical Scien
- Division Of Physics [1427654] Funding Source: National Science Foundation
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While being long in range and therefore weakly specific, electrostatic interactions are able to modulate the stability and folding landscapes of some proteins. The relevance of electrostatic forces for steering the docking of proteins to each other is widely acknowledged, however, the role of electrostatics in establishing specifically funneled landscapes and their relevance for protein structure prediction are still not clear. By introducing Debye-Huckel potentials that mimic long-range electrostatic forces into the Associative memory, Water mediated, Structure, and Energy Model (AWSEM), a transferable protein model capable of predicting tertiary structures, we assess the effects of electrostatics on the landscapes of thirteen monomeric proteins and four dimers. For the monomers, we find that adding electrostatic interactions does not improve structure prediction. Simulations of ribosomal protein S6 show, however, that folding stability depends monotonically on electrostatic strength. The trend in predicted melting temperatures of the S6 variants agrees with experimental observations. Electrostatic effects can play a range of roles in binding. The binding of the protein complex KIX-pKID is largely assisted by electrostatic interactions, which provide direct charge-charge stabilization of the native state and contribute to the funneling of the binding landscape. In contrast, for several other proteins, including the DNA-binding protein FIS, electrostatics causes frustration in the DNA-binding region, which favors its binding with DNA but not with its protein partner. This study highlights the importance of long-range electrostatics in functional responses to problems where proteins interact with their charged partners, such as DNA, RNA, as well as membranes.
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