The nature of persistent interactions in two model β‐grasp proteins reveals the advantage of symmetry in stability

• Published in: Journal of computational chemistry 2021-04, Vol.42 (9), p.600-607
• Main Authors: Bedford, John T., Poutsma, Jennifer, Diawara, Norou, Greene, Lesley H.
• Format: Article
• Language: English
• Subjects: GB1; High temperature; Hydrophobicity; long‐range interactions; MD simulations; Molecular dynamics; persistence; Proteins; SAMP1; Structural stability; Symmetry
• ISSN: 0192-8651; 1096-987X
• DOI: 10.1002/jcc.26477

Two proteins within the β‐grasp superfamily, the B1‐domain of protein G and the small archaeal modifier protein 1, were investigated to elucidate the key determinants of structural stability at the level of individual interactions. These symmetrical proteins both contain two β‐hairpins which form a sheet flanked by a central α‐helix. They were subjected to high temperature molecular dynamics simulations and the detailed behavior of each long‐range interaction was characterized. The results revealed that in GB1 the most stable region was the C‐terminal hairpin and in SAMP1 it was the opposite, the N‐terminal hairpin. Experimental results for GB1 support this finding. In conclusion, it appears that the difference in the location and number of hydrophobic interactions dictate the differential stability which is accommodated due to structural symmetry of the β‐grasp fold. Thus, the hairpins are interchangeable and in nature this lends itself to adaptability and flexibility. The question of how proteins fold is the focus of both computational and experimental research. Resolving this challenging scientific problem would catalyze many profound leaps in basic and medical science. The present research uses molecular dynamics simulations in conjunction with comparative experimental studies to show that persistent long‐range interactions play a critical role in stabilizing native structure and that proteins containing a symmetrical β‐grasp fold have evolutionary flexibility in the stabilization of their 3D structures.