Local motifs in proteins combine to generate global functional moves

Abstract

Literature on the topological properties of folded proteins that has emerged as a field in its own right in the past decade is reviewed. Physics-based construction of coarse-grained models of proteins from knowledge of all-atom coordinates of the average structure is discussed. Once network is thus obtained with the node and link information, local motifs provide plethora of information on protein function. The hierarchical structure of the proteins manifested in the interrelations of local motifs is emphasized. Motifs are also related to modularity of the structure, and they quantify shifts in the landscapes upon conformational changes induced by, e.g. ligand binding. Redundancy emerges as a balance between local and global network descriptors and is related to the collectivity of the protein motions. Introducing weight on links followed by sequential removal of least cohesive contacts allows interactions in proteins to be represented as the superposition of essential and redundant sets. Lack of the former makes the network non-functional, while the latter ensures robust functioning under a wide range of perturbation scenarios.

Protein residue networks from a local search perspective

“…Ref. [34] reports a linear relationship between triangle and diamond motifs in their RINs, and interprets the presence of these local motifs as providing alternative pathways to ensure connectivity as links are made and destroyed when proteins undergo fluctuations at equilibrium. However, their RINs are constructed differently and the diamond motif is also defined differently.…”

“…However, their RINs are constructed differently and the diamond motif is also defined differently. A diamond motif in [34] is a chordless four node cycle. By this definition, nodes b, u, g, and v in Fig.…”

In silico mutational studies of Hsp70 disclose sites with distinct functional attributes

“…For example, a close link between residue fluctuations (B‐factors) of a given protein and the average shortest path length to a residue from all others has been established . The network approach has enabled the study of specific proteins and has helped reveal interesting features not directly evident from the structure or sequence homology . For example, interaction conservation was utilized in phylogenetic analysis of remote homologs of the TIM barrel fold to reveal loop‐based conserved interactions near the active site .…”

“…For example, interaction conservation was utilized in phylogenetic analysis of remote homologs of the TIM barrel fold to reveal loop‐based conserved interactions near the active site . In our current view, the network of interactions in a protein is composed of a set of contacts designated by the spatial arrangement in three‐dimensional space, resulting in a small world network with Poisson distribution of the number of neighbors (also termed degree), allocating necessary contact information for proper functioning under a plethora of external perturbations …”

“…16 In our current view, the network of interactions in a protein is composed of a set of contacts designated by the spatial arrangement in threedimensional space, resulting in a small world network with Poisson distribution of the number of neighbors (also termed degree), allocating necessary contact information for proper functioning under a plethora of external perturbations. 15,17 In this work, we utilize residue networks in conjunction with a systematic residue-by-residue insertion of alanine mutations. We first follow the structural changes caused by the point mutations, and then quantify how these changes are reflected to the local and global network properties.…”