Conservation of intrinsic dynamics in proteins—what have computational models taught us?

• Published in: Current opinion in structural biology 2018-06, Vol.50, p.75-81
• Main Authors: Tiwari, Sandhya P, Reuter, Nathalie
• Format: Article
• Language: English
• Subjects: Algorithms; Catalytic Domain; Computer Simulation; Enzymes - chemistry; Evolution, Molecular; Models, Molecular; Protein Conformation; Proteins - chemistry; Proteins - genetics; Structure-Activity Relationship
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2017.12.001

Clustering of 24 proteins from 5 different superfamilies with the TIM Barrel fold according to their overall flexibility similarity scores; the proteins cluster by superfamilies but their scores remain high overall (0.75 and above) despite little or no evolutionary conservation between them.▪ •Intrinsic flexibility of proteins is more conserved than structure and sequence.•Protein flexibility can be derived from coarse-grained elastic network models.•Flexibility is conserved within structurally similar non-homologous proteins.•Allostery exploits the intrinsic dynamics of protein topology. The intrinsic dynamics of proteins has been suggested to be the most conserved compared to its sequence or structure. As such, the contributing factors to the conservation of dynamics have yet to be determined definitively. Some have suggested that function drives the conservation of protein flexibility, while others have indicated that the overall topology determines protein flexibility patterns. In general, many characteristic features of protein flexibility can be derived from simple coarse-grained models whose success rests on the link between protein local packing density and flexibility. Those models have revealed the evolutionary conservation of protein flexibility and have given us insights into the slow dynamics required for protein function and mechanistic insight into the allosteric effect.