论文部分内容阅读
Proteins are the essential machinery with complicated structural characteristics to carry out delicate biological functions.How do the structure and functions of proteins emerge and evolve efficiently to achieve the colorful natural world? This question is placed in the heart of bioinformatics and biophysics related to proteins.Besides the sequential conservation,the interactions among various biophysical ingredients(energetic stability,geometric constraints of structures,kinetic accessibility of conformations)are also important to build up the comprehensive picture of protein universe.Many successes have been achieved along this line.During the recent decades,it is widely recognized that the disordered segments largely exist in proteins,and take important roles in functional signaling and modulation.The disorder refreshes the Anfinsen view of proteins.Will the disorders contribute to the evolution? In present work,we approach to this topic with simple exact models(2D Lattice Model).For a certain length of proteins,all the structures and sequences are enumerated.Considering the existence of disordered segments,the criterion for protein-like sequences is updated to ensure the uniqueness of the contact map.The resultant protein-like sequences are clustered based on the topology of their contact networks.Each cluster resembles the sequence families with point and ins/del mutations.A SCOP-like architecture of protein universe is discussed based on the models.With these sequences,the evolutionary network is generated based on point mutations.It is found that multiple mutations are necessary to switch between the stable folders,and during the switch,the sequences with disordered segments act as the bridges and guide the switch.With the help of the disordered segments,the transition between different contact maps has weaker energetic penalty.Furthermore,the characteristics of the evolutionary network are analyzed.Each protein(family)has more neighbors comparing to the cases without disordered segments.We also investigated the thermodynamic features of the sequences during the fold switch.It is found that the disordered segments compensate the destroy of the original native interactions.As a remark,different from the previous theory based on bi-stability of landscape,the presence of disordered segments makes the conformational diffusion much easier,which has some functional benefits at some situations.All in all,through our studies,it is suggested that the disorder may smooth the switches between folds and help to realize diverse proteins during evolutionary history.Disorder also offers the flexibility in protein evolution.